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Betel quid chewing is a common practice in many cultures and has been associated with various health risks, including an increased likelihood of developing squamous cell carcinoma (SCC). This case study presents a critical instance of metastatic SCC of the lower lip induced by betel quid chewing. A 45-year-old male with a history of betel quid chewing presented with a persistent and enlarging sore on his lower lip. A biopsy revealed SCC, and subsequent imaging confirmed metastasis to the lungs. This case highlights the potential for betel quid chewing to induce metastatic SCC and emphasizes the need for awareness and cessation of this habit to prevent such severe health outcomes. The aggressive nature of metastatic SCC warrants immediate and effective treatment strategies.

Abstract Aims Social culture concerns and betel quid (BQ) dependence may be the potential reasons for BQ chewing. This study’s purpose was to identify the correlates of reasons for male BQ chewing. Methods We adopted a mixed-methods design. The study was conducted between October 2021 and August 2023 at a medical center of northern Taiwan. The Reasons for Betel-Quid Chewing Scale, Numeric Rating Scale, and Betel Quid Dependence Scale were used to quantitatively assess reasons for BQ chewing, stress, and BQ dependence, respectively. Semi-structured questions were used to interview for qualitative data. Results Among 150 BQ users, the most common reasons for BQ chewing were stimulation, reinforcement, and social/cultural factors. Chewers who reported more pressure to chew were more likely to be younger, have less educational level, be employed, have greater stress, and have more BQ dependence. Content analysis of qualitative data showed three themes: physical and psychological demands, peer pressure, and perceived greater effectiveness. Conclusion Employment was the factor most commonly associated with reasons for BQ chewing and with each construct. Study findings can help healthcare professionals understand reasons for BQ chewing, thereby helping them educate chewers to cope with withdrawal symptoms and successfully quit.

Background Chewing betel quid (BQ) – a preparation commonly containing areca nut and slaked lime wrapped in betel leaf – is entrenched in South Asia. Although BQ consumption during pregnancy has been linked to adverse birth outcomes, its effect on postnatal growth remains largely unexplored. Objective We examined the associations of BQ use during pregnancy with children’s height-for-age and body mass index-for-age z-scores (HAZ and BAZ, respectively) and fat and fat-free mass along with sex-based differences in association in rural Bangladesh. Methods With a prospective cohort design, we assessed BQ use among mothers enrolled in the Preterm and Stillbirth Study, Matlab (n = 3140) with a structured questionnaire around early third trimester. Children born to a subset of 614 women (including 134 daily users) were invited to follow-up between October 2021 and January 2022. HAZ and BAZ were calculated from anthropometric assessment, and fat and fat-free mass were estimated using bioelectric impedance. Overall and sex-specific multiple linear regression models were fitted. Results Growth data were available for 501 children (mean age 4.9 years): 43.3% of them were born to non-users, 35.3% to those using prior to or less-than-daily during the survey, and 21.3% to daily users. No statistically significant associations were observed after adjusting for sex, parity, maternal height and education, and household wealth. Conclusions There was no effect of BQ use during pregnancy on postnatal growth in this study. Longitudinal studies following up those born to heavy users beyond childhood are warranted for capturing long-term implications of prenatal BQ exposure.

Introduction: Areca nut (AN) is the fourth commonly used psychoactive substance, some using it with tobacco (processed AN with tobacco [PANT]). AN–PANT predisposes to a myriad of health disorders. AN–PANT cessation strategies are modeled after tobacco cessation programs, and their efficacies are not evaluated critically. The present study aimed to assess the relative effectiveness of different AN–PANT cessation interventions using a nonparametric network meta-analysis (NMA). Material and Method: An NMA was conducted after registration with Prospero. A systematic search across PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases yielded 137 articles, with 29 duplicates removed. The study population, interventions, comparators, and outcomes framework guided selection criteria for ensuring a robust and relevant analysis. Result: In all, 11 interventions were evaluated across 9 studies involving 12,659 patients. The effect of cessation intervention, as an odds ratio with 95% credibility limits, ranged from 0.30 (0.022–4.01) for a type of behavioral intervention to 10.5 (0.62–229) for Escitalopram. The odds ratio of 95% credible interval of a few studies was only crossing 1. The risk of bias assessment demonstrated the extent of biases within the included trials, contributing to a comprehensive understanding of the wholesome evidence as of the end of 2023. Discussion: The present study underscores the urgent need to re-evaluate the study designs employed in AN/PANT addiction-cessation trials. The present evidence-based insights provided by this NMA could serve as a foundation for designing future trials and guiding clinical decision-making and policy development.

Abstract Oral submucous fibrosis (OSF) is a chronic, progressive condition affecting the oral mucosa associated with areca nut consumption. It leads to restricted tongue movement, loss of papillae, blanching and stiffening of the mucosa, difficulty in opening the mouth, and challenges in eating due to inflammation and fibrosis. This report presents a rare case of oropharyngeal stenosis secondary to OSF in a 43-year-old male with a history of chewing betel nut. A surgical procedure similar to Uvulopalatopharyngoplasty was performed to excise the submucous oropharyngeal stenosis and to reconstruct the uvula, palatoglossal arch, and palatopharyngeal arch. At 8 years postoperatively, the patient exhibited a normal mouth opening and oropharyngeal aperture.

Introduction: Areca nut (AN) is the fourth commonly used psychoactive substance, some using it with tobacco (processed AN with tobacco [PANT]). AN–PANT predisposes to a myriad of health disorders. AN–PANT cessation strategies are modeled after tobacco cessation programs, and their efficacies are not evaluated critically. The present study aimed to assess the relative effectiveness of different AN–PANT cessation interventions using a nonparametric network meta-analysis (NMA). Material and Method: An NMA was conducted after registration with Prospero. A systematic search across PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases yielded 137 articles, with 29 duplicates removed. The study population, interventions, comparators, and outcomes framework guided selection criteria for ensuring a robust and relevant analysis. Result: In all, 11 interventions were evaluated across 9 studies involving 12,659 patients. The effect of cessation intervention, as an odds ratio with 95% credibility limits, ranged from 0.30 (0.022–4.01) for a type of behavioral intervention to 10.5 (0.62–229) for Escitalopram. The odds ratio of 95% credible interval of a few studies was only crossing 1. The risk of bias assessment demonstrated the extent of biases within the included trials, contributing to a comprehensive understanding of the wholesome evidence as of the end of 2023. Discussion: The present study underscores the urgent need to re-evaluate the study designs employed in AN/PANT addiction-cessation trials. The present evidence-based insights provided by this NMA could serve as a foundation for designing future trials and guiding clinical decision-making and policy development. [ABSTRACT FROM AUTHOR]

Oral submucous fibrosis (OSF) is a chronic, progressive condition affecting the oral mucosa associated with areca nut consumption. It leads to restricted tongue movement, loss of papillae, blanching and stiffening of the mucosa, difficulty in opening the mouth, and challenges in eating due to inflammation and fibrosis. This report presents a rare case of oropharyngeal stenosis secondary to OSF in a 43-year-old male with a history of chewing betel nut. A surgical procedure similar to Uvulopalatopharyngoplasty was performed to excise the submucous oropharyngeal stenosis and to reconstruct the uvula, palatoglossal arch, and palatopharyngeal arch. At 8 years postoperatively, the patient exhibited a normal mouth opening and oropharyngeal aperture. [ABSTRACT FROM AUTHOR]

Introduction: Betel quid (BQ) is globally the fourth most consumed psychoactive substance. It is consumed by an estimated 600 million people worldwide, accounting for nearly 8% of the world's population. There have been very few studies assessing chewers' motivation to quit. Objectives: In the current study, we sought to understand the relationship between several cessation-relevant variables and chewers' motivation to quit. Hypotheses: Based on analogous research on cigarette smoking, we hypothesized that the following cessation-relevant variables would be associated with motivation to quit: health risk perceptions, number of chews per day, cost, degree of BQ dependence, withdrawal symptoms, number of quit attempts, reasons for use, personal health improvement, and type of BQ chewed. Methods: A total of 351 adult BQ chewers from Guam participated in the survey and served as the sample for the analyses. Results: Majority of chewers want to quit and intend to quit. Chewers relatively high in motivation to quit evinced greater health risk perceptions of BQ chewing, greater perceived health benefits to quitting, and a greater number of past quit attempts, compared to those relatively low in motivation to quit. Conclusions: Understanding which factors are associated with chewers' motivation to quit can be helpful for designing BQ cessation programs. The results suggest that BQ cessation programs could be improved by an increased emphasis on information about the negative health effects of BQ chewing and relapse-prevention. [ABSTRACT FROM AUTHOR]

Introduction: Habitual betel quid chewing, a tobacco product, is a leading cause of oral cancer in Asia–Pacific countries where this practice is most prevalent. However, it is not well understood whether betel quid chewing is also a cause of adverse cardiovascular outcomes. To address this gap, we conducted a systematic literature review of peer‐reviewed published studies evaluating the association between habitual betel quid use on the risk of adverse cardiovascular outcomes. Methods: We searched PubMed for studies assessing the correlation between betel quid chewing and cardiovascular health. We included studies if (i) they included human subjects; (ii) were peer‐reviewed articles in indexed journals; and (iii) were in English. We extracted data from eligible studies and stratified them by geographical location, study designs and cardiovascular outcomes. Finally, we did a narrative synthesis of the data to identify adverse cardiovascular outcomes associated with chronic betel quid use. Findings: We reviewed data from 19 studies that met the inclusion criteria. Habitual betel quid chewing was associated with hypertension, atherosclerosis, inflammation and ischaemic heart disease. In addition, betel quid use was a risk factor for arrhythmias. Interestingly, betel quid use was an independent risk factor for cardiovascular disease in women. Long‐term betel quid consumption was associated with higher risks for all‐cause mortality and increased overall cardiovascular risk. Conclusions: Habitual betel quid chewing is an important cardiovascular risk factor in populations where the practice is prevalent. [ABSTRACT FROM AUTHOR]

BackgroundChewing tobacco consumption has become a major public health issue in India. The incidence of oral cancer is increasing in India, especially among young adults.AimThe objective of this study was to ascertain the prevalence of chewing tobacco consumption and its association with the occurrence of oral mucosal lesions.MethodsA cross-sectional survey was conducted among 1,209 patients who reported to the Department of Oral Medicine and Radiology at Vyas Dental College, Jodhpur. A structured questionnaire was used to collect information on patients’ personal information such as demographic details, tobacco use, and other adverse habits. A single calibrated investigator performed a clinical examination of lesions on the oral mucosa, and the diagnosis was further validated.ResultsThe majority of the participants were men (81.8%) in the age range of 26–35 years. A habit of chewing a combination of tobacco and areca nut (48.2%) was more prevalent. More than 36% of the participants consumed tobacco in a processed form (90%), at least four times a day. It was observed was 25% of the participants were suffering from tobacco pouch keratosis.ConclusionChewing tobacco was significantly associated with the development of oral mucosal lesions, particularly among men and those belonging to lower socio-economic groups. Along with targeted public health interventions on tobacco cessation, it is essential to change the cultural norms associated with the habit of chewing tobacco and implement strict chewing tobacco control laws in the community and workplaces.

Betel quid (BQ), a prevalent social habit in Asia, is often used without awareness of its harmful effects. This study explored the impact of BQ chewing on hyperglycemia among diabetic patients in northeastern Bangladesh. Specifically, this study focused on the role of areca nut, a key addictive component in BQ, in influencing hyperglycemia. Random blood glucose (RBG) tests were conducted on 961 diabetic patients, alongside lifestyle data, from August 2018 to February 2019 at Sylhet Diabetic Hospital, Bangladesh. Statistical analyses, including t-tests, Analysis of the variance (ANOVA), Fisher's exact test, and Multivariate regression, were employed to assess RBG status in BQ chewer vs. non-chewer. BQ chewers had higher RBG levels than non-chewers (263.3 ± 4.768 vs. 251.0 ± 5.915). Notably, raw areca nut users in the BQ group had significantly higher RBG levels than dry nut users (278.0 ± 8.790 vs. 252.1 ± 6.835 mg/dl), with up to 50 times more hyperglycemic effect. BQ chewing was associated with elevated RBG levels across different demographic and lifestyle groups. Lack of awareness was also prevalent among BQ chewers while individuals with desk jobs showed higher RBG levels. In conclusion, diabetic BQ chewers experience elevated hyperglycemia levels, highlighting the. urgent need to discourage BQ use for effective diabetes management. [ J Adv Biotechnol Exp Ther 2024; 7(3.000): 460-471]

Introduction Global perspective Public health Conclusion The association between areca nut consumption and oral cancer has been a subject of increasing concern in global public health.Areca nut, often chewed in various forms such as betel quid, is deeply rooted in cultural practices across Asia and other parts of the world. Epidemiological studies consistently reveal a significant correlation between areca nut use and the incidence of oral cancer, emphasizing the need for targeted preventive measures. The complex interplay of areca nut's bioactive compounds, particularly arecoline, with cellular processes, contributes to the initiation and progression of oral carcinogenesis. Mechanistic insights into the genotoxic and cytotoxic effects of its components underscore the urgency for comprehensive public health interventions.Efforts to address this public health challenge involve multidisciplinary approaches, encompassing education, policy implementation, and behavioral interventions. Understanding the socio‐cultural factors influencing areca nut consumption is pivotal for designing effective awareness campaigns and cessation programs.As oral cancer remains a significant global health burden, unraveling the nuanced relationship between areca nut and its role in oral carcinogenesis is crucial for advancing preventive strategies and mitigating the impact of this modifiable risk factor. [ABSTRACT FROM AUTHOR]

Simple Summary: Trismus is a common complication in oral cancer patients that may influence surgical outcomes. This retrospective matched cohort analysis examined the influence of preoperative trismus on survival outcomes in 40 male Taiwanese oral cancer patients undergoing transoral robotic surgery (TORS). Through 1:1 propensity score matching, 20 trismus patients were compared to 20 non-trismus controls. TORS demonstrated comparable short-term surgical outcomes in trismus patients compared to non-trismus patients. There were no significant differences between groups in operation time, blood loss, margin status, flap reconstruction rates, duration of nasogastric tube feeding, or length of hospital stay. Analysis of long-term oncological outcomes demonstrated similar 5-year disease-free survival between groups, indicating comparable tumor control. However, trismus patients experienced significantly poorer 5-year overall survival. After adjusting for confounders, trismus independently conferred a 13-fold higher long-term mortality risk. Ultimately, this study highlights preoperative trismus as a harbinger of non-inferior short-term surgical outcomes, but diminished long-term survival in oral cancer patients treated robotically, even among those with equivalent tumor persistence following surgery. Further research should explore mechanisms linking trismus to mortality and approaches to improve outcomes in this population. Trismus, defined as restricted mouth opening, is a common complication among Taiwanese oral cancer patients, especially those who chew betel quid. However, the impact of trismus on survival outcomes in oral cancer patients undergoing transoral robotic surgery (TORS) is unclear. This study aimed to investigate the associations between trismus and surgical outcomes in Taiwanese male oral cancer patients treated with TORS. We conducted a retrospective propensity score-matched cohort study of 40 Taiwanese male oral cancer patients who underwent TORS between 2016 and 2022. Overall, 20 patients with trismus were matched to 20 patients without trismus. TORS achieved similar operative and short-term clinical outcomes in trismus patients to non-trismus patients. There were no significant differences between groups in operation time, blood loss, margin status, flap reconstruction rates, duration of nasogastric tube feeding, or length of hospital stay. Kaplan–Meier and Cox proportional hazard regression analyses were performed to compare overall survival (OS) and disease-free survival (DFS) between the two groups. The overall survival (OS) rate at three years was significantly lower in patients with trismus than those without trismus (27.1% vs. 95.0%, log-rank p = 0.02). However, there was no significant difference in disease-free survival (DFS) rates between the trismus and non-trismus groups (36.6% vs. 62.7%, log-rank p = 0.87). After adjusting for confounders, trismus was independently associated with a 13-fold increased risk of mortality (adjusted HR 12.87, 95% CI 1.55–106.50, p < 0.05). In conclusion, trismus appears to be an independent prognostic factor for reduced long-term OS in Taiwanese male oral cancer patients undergoing TORS, though short-term surgical outcomes were non-inferior in the trismus patients. Further research is warranted to clarify the mechanisms linking trismus and survival in this population. [ABSTRACT FROM AUTHOR]

BackgroundBetel quid (BQ) chewing is a prevalent habit in the Asian and Pacific regions. It is deeply intertwined within cultural customs, and has been reported to result in oral potentially malignant disorders (OPMDs) and malignant disorders (MDs).ObjectiveWe aim to present a summative and broad overview of the burden that BQ chewing has imposed on the residents of the Southeast Asian, Pacific, and Australasian regions, allowing us to quantify the level of impact it is currently causing on the risk of people developing oral cancer.MethodsThis scoping review and meta-analysis screened databases such as PubMed, MEDLINE, and Google Scholar for publications that investigated the association between BQ and OPMDs and MDs. The search strategy involved MeSH headings relating to BQ, OPMDs, and MDs, and a search for results during the period between January 2010 and June 2023 within the set geographical boundaries of the Southeast Asian and Pacific regions. This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement for Scoping Reviews (PRISMA-ScR). R software was used to screen outliers. The included studies were further analysed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.ResultsNine articles (n = 19,312 participants) presented odds ratio outcomes from 11 regionally different study groups. We indicated a strong correlation between BQ chewing and the increased risk of OMPDs and MDs. The risk was quantified through meta-analyses with an odds ratio (OR) of 8.18 (5.27–12.72) and an increased OR of 9.93 (7.36–13.39) when the outlier was removed. BQ chewing was further identified within various Australian communities and discovered to be produced locally in North Queensland.DiscussionA meta-analysis of two outcomes revealed substantial heterogeneity and minor evidence of publication bias, thus the association effect was included with and without these articles. The overall GRADE quality of evidence ranged from moderate to very high and highlighted five studies with a high level of imprecision.ConclusionThe lingering high prevalence of BQ in the Southeast Asia and Pacific regions, as well as its rising acceptance among non-ethnic Australians, is alarming and requires prompt and rigorous intervention to prevent the risk of oral cancer.Systematic Review RegistrationPROSPERO (CRD42023429694).

Scientometric analysis is a useful tool that utilizes bibliometric data to measure scientific output of a disease or region in a particular field. In this report, we comprehensively provide bibliometric characteristics of all the papers on betel quid (BQ)-related cancer and precancerous lesions. There are 1403 papers on BQ-related cancer and precancerous lesions published until 2022 in the Scopus database. China (mainland and Taiwan region), India, United States, and United Kingdom contribute 1214 (86.5%) papers and 34,120 (91.9%) citations of all the papers. The number (457), citations (14,573), and h index (60) of the papers originated from Taiwan region stably remain in the first. The most frequent research keyword is arecoline, followed by drug, prevalence, metabolism, carcinogenesis, and pathology. Areca nut and BQ cessation program by Taiwan government has demonstrated a significant positive impact on oral cancer prevention. Collectively, the scientific output of BQ-related cancer and precancerous field represents distinct regional characteristic. BQ-related cancer prevention is still a long way off. Encouragingly, Taiwan region is well ahead in this way.

Background: Oral cancer is one of the most common types of cancer worldwide, and India shows a high incidence of oral squamous cell carcinoma (OSCC) cases. Kerala accounts for a sizeable number of these cases, most of which can be attributed to the deleterious habits prevalent in a vast majority of the population. A comprehensive descriptive-prospective study was done in our institution over 18 months to identify the possible risk factors, to describe the clinical and sociodemographic variables of OSCC, and to understand the burden of this dreaded disease in the North Kerala population. Materials and Methods: Data collection was done using a structured pro forma. The data were tabulated and organized; uni- and bivariate analysis were performed along with cross-tabulations for various parameters and relevant variables. A total of 243 histopathologically confirmed cases of OSCC during 18 months comprised the sample in this study. Results: Among the 243 cases, 220 patients had deleterious habits. Betel chewing was the most predominant habit. Buccal mucosa was the commonly affected site. Twenty-three patients had no history of any habits. Majority of the patients presented in stage 3 and 4 of the disease. Moderately differentiated squamous cell carcinoma was the major histologic type. Conclusion: The majority of the patients had clinical lesions corresponding to the habit usage, showing a low awareness of tobacco cessation and intervention programs and a high burden of OSCC in the North Kerala population. [ABSTRACT FROM AUTHOR]

Abstract Background Betel quid (BQ) chewing is associated with poor oral hygiene, psychological impairment, and acute and long-term addictive effects, resulting in worse oral-related quality of life (OHRQoL). The purpose of this study was to characterize the factors associated with OHRQoL among BQ users receiving oral mucosal screening. Methods A cross-sectional study was conducted. Data were collected by random sampling of BQ users who visited outpatient departments receiving oral mucosal screening in a medical center Taiwan. The oral health assessment tool, the state anxiety inventory, the betel quid dependence scale, and the oral health impact profile were used to measure oral health status, anxiety, BQ dependence, and OHRQoL, respectively. Pearson’s product-moment coefficient was used to examine the relationship between OHRQoL and the selected independent variables. Independent-samples t-test was used to compare OHRQoL by annual family income, the presence of chronic disease, and BQ dependence. Hierarchical multiple linear regression analysis was used to identify factors associated with OHRQoL. Results A total of 175 BQ users were surveyed. Factors associated with OHRQoL included oral health status, anxiety, and BQ dependence. BQ users reporting low oral health status, greater anxiety, and more BQ dependence were more likely to have worse OHRQoL. Conclusions Poor oral health status, anxiety, and BQ dependence negatively impact on OHRQoL among patients with BQ use receiving oral mucosal screening.

Areca nut and slaked lime, with or without tobacco wrapped in Piper betle leaf, prepared as betel quid, is extensively consumed as a masticatory product in many countries across the world. Betel Quid can promote the malignant transformation of oral lesions as well as trigger benign cellular and molecular changes. In the oral cavity, it causes changes at the compositional level in oral microbiota called dysbiosis. This dysbiosis may play an important role in Oral Cancer in betel quid chewers. The abnormal presence and increase of bacteria Fusobacterium nucleatum, Capnocytophaga gingivalis, Prevotella melaninogenica, Peptostreptococcus sp., Porphyromonas gingivalis, and Streptococcus mitis in saliva and/or other oral sites of the cancer patients has attracted frequent attention for its association with oral cancer development. In the present review, the authors have analysed the literature reports to revisit the oncogenic potential of betel quid and oral microbiome alterations, evaluating the potential of oral microbiota both as a driver and biomarker of oral cancer. The authors have also shared a perspective that the restoration of local microbiota can become a potentially therapeutic or prophylactic strategy for the delay or reversal of lip and oral cavity cancers, especially in high-risk population groups. [ABSTRACT FROM AUTHOR]

Scientometric analysis is a useful tool that utilizes bibliometric data to measure scientific output of a disease or region in a particular field. In this report, we comprehensively provide bibliometric characteristics of all the papers on betel quid (BQ)-related cancer and precancerous lesions. There are 1403 papers on BQ-related cancer and precancerous lesions published until 2022 in the Scopus database. China (mainland and Taiwan region), India, United States, and United Kingdom contribute 1214 (86.5%) papers and 34,120 (91.9%) citations of all the papers. The number (457), citations (14,573), and h index (60) of the papers originated from Taiwan region stably remain in the first. The most frequent research keyword is arecoline, followed by drug, prevalence, metabolism, carcinogenesis, and pathology. Areca nut and BQ cessation program by Taiwan government has demonstrated a significant positive impact on oral cancer prevention. Collectively, the scientific output of BQ-related cancer and precancerous field represents distinct regional characteristic. BQ-related cancer prevention is still a long way off. Encouragingly, Taiwan region is well ahead in this way. [ABSTRACT FROM AUTHOR]

Understanding the carcinogenesis mechanism of different carcinogenic agents is paramount for implementing preventive and therapeutic strategies for cancer. Hence, an appropriate simulation of the clinical situation in preclinical studies should be the prime mandate for reaching the validated and pragmatic conclusion. In Asian and Southeast Asian countries, one of the most common etiological agents for oral squamous cell carcinoma (OSCC) is the consumption of betel quid (BQ) with and without tobacco. BQ is marketed in the form of a mixture of various ingredients. It is quite conceivable that when BQ is placed or chewed in the oral cavity, all the carcinogenic components released from different agents get mixed and forms an amalgamation of carcinogens. To further add to the complexity, oral microbial flora also becomes part and parcel of this amalgamation. We envisage the interactions of various carcinogens with each other and the salivary components and microbial flora. However, this clinical scenario is not exactly simulated in various in-vitro experimental studies published in the literature. To better understand the oral carcinogenesis mechanism, it becomes imperative to consider the aforementioned fact in mind while studying carcinogens for oral cancer. In the present commentary, we have made an effort to discuss the amalgamation of the carcinogens in the oral cavity and propose the possible preclinical model to study carcinogens associated with OSCC.

Background: Smoking, drinking and chewing tobacco product, common habits in India have been positively associated with oral lesions such as oral submucous fibrosis (OSMF), Leukoplakia, and oral lichen planus (OLP). Materials and methods: A total of 160 patients of both genders with age above 35-60 year were divided into four groups of Leukoplakia, OSMF, OLP and control group each. Detailed case history, habit history, habit score was recorded. Results: In this study it was found that OSMF patients with combined habit of smoking tobacco with quid usage patterns, Leukoplakia patients with smoking(beedi) and OLP patients with combined tobacco usage habits and quid usage habits showed presence of advance stages of disease. Conclusion: This study emphasised that deleterious habits as not only a predisposing factor in the occurrence but plays crucial role in progression to severe form of OSMF and Leukoplakia. [ABSTRACT FROM AUTHOR]

The physical and chemical properties of various constitutional ingredients of betel quid (BQ) are well known in the literature. However, BQ as a whole has been rarely investigated for identifying its physical properties that can impact and modulate the disease progression of various pathologies, mainly oral submucous fibrosis (OSMF). It is quite conceivable that in the oral cavity environment, the amalgamated BQ might absorb saliva by virtue of its hygroscopic properties. As a proof of concept, we developed a methodology to quantify the hygroscopicity of the ‘whole BQ’ when it is mixed with saliva. To the best of our knowledge, this is the first study to report and quantify the hygroscopicity of BQ when mixed with saliva, and this forms a proof of concept for future implications in the pathogenesis of various pathologies.

Betel quid and areca nut are complex mixture carcinogens, but little is known about whether their derived single-agent arecoline or arecoline N-oxide (ANO) is carcinogenic, and the underlying mechanisms remain unclear. In this systematic review, we analyzed recent studies on the roles of arecoline and ANO in cancer and strategies to block carcinogenesis. In the oral cavity, flavin-containing monooxygenase 3 oxidizes arecoline to ANO, and both alkaloids conjugate with N-acetylcysteine to form mercapturic acid compounds, which are excreted in urine, reducing arecoline and ANO toxicity. However, detoxification may not be complete. Arecoline and ANO upregulated protein expression in oral cancer tissue from areca nut users compared to expression levels in adjacent normal tissue, suggesting a causal relationship between these compounds and oral cancer. Sublingual fibrosis, hyperplasia, and oral leukoplakia were diagnosed in mice subjected to oral mucosal smearing of ANO. ANO is more cytotoxic and genotoxic than arecoline. During carcinogenesis and metastasis, these compounds increase the expression of epithelial–mesenchymal transition (EMT) inducers such as reactive oxygen species, transforming growth factor-β1, Notch receptor-1, and inflammatory cytokines, and they activate EMT-related proteins. Arecoline-induced epigenetic markers such as sirtuin-1 hypermethylation, low protein expression of miR-22, and miR-886-3-p accelerate oral cancer progression. Antioxidants and targeted inhibitors of the EMT inducers used reduce the risk of oral cancer development and progression. Our review findings substantiate the association of arecoline and ANO with oral cancer. Both of these single compounds are likely carcinogenic to humans, and their mechanisms and pathways of carcinogenesis are useful indicators for cancer therapy and prognosis. [ABSTRACT FROM AUTHOR]

A disintegrin and metalloproteinase domain‐containing protein 10 (ADAM‐10) involves in the tumour progression, but the impacts of single‐nucleotide polymorphism (SNP) of ADAM‐10 on oral squamous cell carcinoma (OSCC) remain unclear. The aim of this study was to investigate the influence of SNP of ADAM‐10 on the clinical features of OSCC in male Taiwanese. Five loci of ADAM‐10 SNPs including rs653765 (C/T), rs2305421 (A/G), rs514049 (A/C), rs383902 (T/C) and rs2054096 (A/T) were genotyped by TaqMan allelic discrimination in 1138 OSCC patients and 1199 non‐OSCC individuals. The ADAM‐10 SNP rs2305421 GG (AOR: 1.399, 95% CI: 1.045–1.874, p = 0.024) and G allele (AOR: 1.170, 95% CI: 1.012–1.351, p = 0.034) illustrated a significantly higher genotypic frequencies in the OSCC group compared to the distribution of the ADAM‐10 SNP rs2305421 AA wild type. In the subgroup analysis, the ADAM‐10 SNP rs383902 TC+CC was significantly correlated to tumour size larger than T2 in betel quid chewer (AOR: 1.375, 95% CI: 1.010–1.872, p = 0.043), while the ADAM‐10 SNP rs653765 CT+TT was significantly associated with tumour size larger than T2 in cigarette smoker (AOR: 1.346, 95% CI: 1.023–1.772, p = 0.034). The results from The Cancer Genome Atlas revealed highest ADAM‐10 mRNA level in T2 stage of current smokers with head and neck squamous cell carcinoma (HNSCC). In conclusions, the ADAM‐10 SNP rs2305421 G allele is associated with the presence of OSCC, and the ADAM‐10 SNP rs383902 TC+CC and ADAM‐10 SNP rs653765 CT+TT correlates to large tumour size in specific conditions. [ABSTRACT FROM AUTHOR]

A fatal disorder named oral submucous fibrosis (OSMF) is marked by the oral submucosa's progressive fibrosis. OSMF is distinguished by aberrant collagen deposition. In 1.5-15% of patients, it's a precancerous condition that progresses to a malignant tumour. Although nutrient deficiencies and immunological procedures could perform a role in pathogenesis, epidemiological evidence suggests that betel nut quid (which contains guvacine, arecoline, guvacoline, arecaidine, and chavibetol) contains areca nut, slaked lime, tobacco, is a significant risk factor for OSMF. Submucous fibrosis, xerostomia, ulceration, a burning sensation, and a limited mobility of the mouth are among the symptoms. The patient's quality of life is seriously affected by each of these components. The present article gives a broad overview of OSMF from a molecular viewpoint and describes what has been learned about its underlying causes, methods of diagnosis, and available treatments. Along with active therapy for OSMF, prophylaxis is essential, and this section gives a quick review of its treatment. [ABSTRACT FROM AUTHOR]

Background: Areca nut (AN) is one of the world's most widely used drugs, especially in Asia-Pacific, causing dependence and multiple adverse health impacts. The International Agency for Research on Cancer (IARC) has classified it as a type-1 carcinogen. Despite evidence of harms, its use is culturally ingrained in many regions worldwide; harm perception is low; and the availability of intervention strategies is limited. Methods: To identify the range and efficacy of interventional studies on AN use cessation, a narrative review of studies published between 1990 and 2021 was undertaken using selected electronic databases (PubMed, Embase, and Scopus). Results: Three types of interventions were identified: educational, psychological, and pharmacological. Overall, educational interventions significantly enhanced knowledge regarding harms related to AN use. Some psychological interventions reported enhancement of motivation to quit as well as helped in reduction/cessation of AN use. Two pharmacological studies on psychiatric patients with depressive disorders and AN use found that antidepressants helped in reducing/cessation of AN use. Conclusion: Overall, the number of interventional studies on AN cessation is limited, and most studies have measured the short-term effects of the intervention. The role of pharmacotherapeutic interventions needs to be evaluated for AN cessation, and evidence-based psychosocial interventions need to be developed for AN cessation. Furthermore, longitudinal research using adequate sample sizes and longer follow-up durations are needed to establish interventions in this important area. [ABSTRACT FROM AUTHOR]

Betel quid (BQ) is commonly used in the Asia-Pacific region. Disulfiram is prescribed for people with alcohol use disorders (PwAUDs) after the completion of detoxification as an alternative to rehabilitation. This prospective observational study reported the aversive reactions and common symptoms of disulfiram and BQ in PwAUDs. Participants included PwAUDs admitted to the psychiatric ward at the Jigme Dorji Wangchuck National Referral Hospital for detoxification, who were on Disulfiram and using BQ at the same time. Aversive reactions between disulfiram and BQ were observed for 100 patients over a year. Twenty participants showed aversive reactions between BQ and disulfiram. Common symptoms included sweating, diarrhea, dizziness, tremors, palpitations, shortness of breath, nausea and vomiting, and headache. Since PwAUDs in Bhutan are inducted on disulfiram after detoxification, and most use BQ simultaneously, this study will help inform health care providers to educate people about the aversive reactions of disulfiram and BQ. [ABSTRACT FROM AUTHOR]

Background: The Betel Nut Intervention Trial (BENIT) is the first known randomized controlled intervention trial designed to help minority Pacific Islanders in Guam and Saipan quit chewing the carcinogenic Areca catechu nut (AN). We report the BENIT's saliva bioverification results against the self‐reported chewing status ("quitter" or "chewer") at day 22 follow‐up. Material and Methods: AN‐specific (arecoline, arecaidine, guvacoline, and guvacine) and tobacco‐specific (nicotine, cotinine, and hydroxycotinine) alkaloids were analyzed in saliva from 176 BENIT participants by an established and sensitive liquid chromatography mass spectrometry‐based assay. Results: The combined four AN alkaloid levels decreased from baseline in quitters (n = 50) and chewers (n = 108) by 32% and 9%, respectively. In quitters, decreases were significant for arecoline (p = 0.044)—the most prominent AN alkaloid, along with arecaidine (p = 0.042) and nicotine (p = 0.011). In chewers, decreases were significant only for hydroxycotinine (p = 0.004). Similar results were obtained when quitters and chewers were stratified by treatment arm. Discussion: Salivary AN alkaloid levels generally agreed with self‐reported chewing status, which suggests the former can be used to verify the latter. Conclusion: Our results can help to objectively evaluate compliance and program effectiveness in AN cessation programs. [ABSTRACT FROM AUTHOR]

Background: Altered cerebral cortex's structural organization has been found in individuals with betel quid dependence (BQD). However, the neurological underpinnings of the BQD-related abnormalities in cortical thickness and brain circuitry deficit are largely unknown., Objective: This study aimed to investigate potential abnormalities of brain circuitry in the cortical thickness of BQD individuals by applying the surface-based morphometry (SBM) method., Design: Cross-sectional study., Methods: High spatial resolution, three-dimensional T1-weighted structural imaging data were collected from 53 individuals with BQD and 37 healthy controls (HCs) who were similar to the BQD group in terms of age, sex, and educational level. The SBM method was applied to analyze the cortical thickness alterations in BQD-related areas. Independent-samples t -test was used to assess the cortical thickness difference between the two groups. Pearson correlation analysis was used to investigate the correlation between cortical thickness changes and clinical characteristics, including BQD scale scores and duration of BQD., Results: The BQD group had a higher cortical thickness than the HC group at the lateral orbitofrontal ( t = 4.703, p = 0.0028) and pars opercularis ( t = 3.602, p = 0.0403) clusters in the right cerebral hemisphere, with age, sex, and education duration as covariates ( p < 0.05, Monte Carlo). There were no significant differences in age, sex, or education duration-adjusted cortical thickness of the left cerebral hemisphere between BQD chewers and HCs ( p > 0.05, Monte Carlo). Correlation analysis revealed that the cortical thickness of the right pars opercularis was negatively correlated with the BQD duration ( r = 0.047). The cortical thickness of the right lateral orbitofrontal cluster was not significantly correlated with Betel Quid Dependence Scale (BQDS) or BQD duration ( p = 0.047). The cortical thickness of the right lateral orbitofrontal cluster was not significantly correlated with Betel Quid Dependence Scale (BQDS) or BQD duration ( p > 0.05)., Conclusion: This study demonstrated that BQD might be associated with changes in the orbitofrontal and pars opercularis cortical thickness, which may be related to the neurobiological basis of BQD., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2024.)

Areca nut (AN) is consumed by millions of people for its therapeutic and psychoactive effects, making it one of the most widely self-administered psychoactive substances in the world. Even so, AN use/abuse is associated with myriad oral and systemic side effects, affecting most organ systems in the body. Alkaloids abundant in the nut (e.g. arecoline, arecaidine, guvacoline, and guvacine), collectively called the areca alkaloids, are presumably responsible for the major pharmacological effects experienced by users, with arecoline being the most abundant alkaloid with notable toxicological properties. However, the mechanisms of arecoline and other areca alkaloid elimination in humans remain poorly documented. Therefore, the purpose of this review is to provide an in-depth review of areca alkaloid pharmacokinetics (PK) in biological systems, and discuss mechanisms of metabolism by presenting information found in the literature. Also, the toxicological relevance of the known and purported metabolic steps will be reviewed. In brief, several areca alkaloids contain a labile methyl ester group and are susceptible to hydrolysis, although the human esterase responsible remains presumptive. Other notable mechanisms include N-oxidation, glutathionylation, nitrosamine conversion, and carbon–carbon double-bond reduction. These metabolic conversions result in toxic and sometimes less-toxic derivatives. Arecoline and arecaidine undergo extensive metabolism while far less is known about guvacine and guvacoline. Metabolism information may help predict drug interactions with human pharmaceuticals with overlapping elimination pathways. Altogether, this review provides a first-of-its-kind comprehensive analysis of AN alkaloid metabolism, adds perspective on new mechanisms of metabolism, and highlights the need for future metabolism work in the field. [ABSTRACT FROM AUTHOR]

Consumption of areca nut alone, or in the form of betel quid (BQ), has negative health effects and is carcinogenic to humans. Indonesia is one of the largest producers of areca nuts worldwide, yet little is known about the biomolecular composition of Indonesian areca nuts and BQs. We have recently shown that phenolic and alkaloid content of Indonesian BQs exhibits distinct geographical differences. Here, we profiled for the first time the metabolomics of BQ constituents from four regions of Indonesia using non-targeted gas chromatography–mass spectrometry (GC–MS) analysis. In addition to well-known alkaloids, the analysis of small-molecule profiles tentatively identified 92 phytochemicals in BQ. These included mainly benzenoids and terpenes, as well as acids, aldehydes, alcohols, and esters. Safrole, a potentially genotoxic benzenoid, was found abundantly in betel (Piper betle) inflorescence from West Papua and was not detected in areca nut samples from any Indonesian region except West Papua. Terpenes were mostly detected in betel leaves and inflorescence/stem. Areca nut, husk, betel leaf, the inflorescence stem, and BQ mixture expressed distinctive metabolite patterns, and a significant variation in the content and concentration of metabolites was found across different geographical regions. In summary, this was the first metabolomic study of BQs using GC–MS. The results demonstrate that the molecular constituents of BQs vary geographically and suggest that the differential disease-inducing capacity of BQs may reflect their distinct chemical composition. [ABSTRACT FROM AUTHOR]

Natural products and traditional ethnomedicines are of great effect in therapeutics. Such types of medicine have been practiced in certain areas of the world to treat different health conditions. This pilot investigation aims to review the cumulative health effect of addendums used in betel quid such as areca nut, lime, and tobacco-associated betel quid chewing and without tobacco-associated chewing. This review shows that betel leaf extract and its essential oil could inhibit growth of microbes and damage different gram-positive and gram-negative bacteria as well as various fungus species. Some studies concluded that the combination of Piper leaves essential oil with antibiotics have potential effect on oral microorganisms. Long-term consumption of betel quid with tobacco is known to cause cancer, chromosomal aberrations, and pharynx tumors. However, consumption of betel leaf without tobacco has health benefits because of ethnomedicinal properties. Its essential is oil utilized as raw material for perfumes and mouth fresheners manufacturing. Scientific researches on this plant revealed that it possesses many beneficial activities to be used for developing novel drugs. However, compounds of betel leaves have beneficial natural antioxidant. Chewing and intake of leaves have effect on moving parts of salivary gland which is the main step of digestion. Its components also act as heartbeat regulators in relaxing the blood vessels to reduce hypertension. So this review discussed the natural compounds of betel leaves which is used as traditional medicine to further develop drug discovery. [ABSTRACT FROM AUTHOR]

The use of areca nuts (areca) in the form of betel quids constitutes the fourth most common addiction in the world, associated with high risk for oral disease and cancer. Areca is a complex natural product, making it difficult to identify specific components associated with the addictive and carcinogenic properties. It is commonly believed that the muscarinic agonist arecoline is at the core of the addiction. However, muscarinic receptor activation is not generally believed to support drug-taking behaviour. Subjective accounts of areca use include descriptions of both sedative and stimulatory effects, consistent with the presence of multiple psychoactive agents. We have previously reported partial agonism of α4-containing nicotinic acetylcholine receptors by arecoline and subsequent inhibition of those receptors by whole areca broth. In the present study, we report the inhibition of nicotinic acetylcholine receptors and other types of neurotransmitter receptors with compounds of high molecular weight in areca and the ability of low molecular weight areca extract to activate GABA and glutamate receptors. We confirm the presence of a high concentration of GABA and glutamate in areca. Additionally, data also indicate the presence of a dopamine and serotonin transporter blocking activity in areca that could account for the reported stimulant and antidepressant activity. Our data suggest that toxic elements of high molecular weight may contribute to the oral health liability of betel quid use, while two distinct low molecular weight components may provide elements of reward, and the nicotinic activity of arecoline contributes to the physical dependence of addiction. [ABSTRACT FROM AUTHOR]

Areca nut chewing is one of the major risk factors for oral cancer, with large-magnitude risks reported in studies comparing betel quid chewers and never users, and it has been evaluated as a group 1 carcinogen by the International Agency for Research on Cancer. Data from a high-quality meta-analysis examining risk estimates are presented in summary form with additional information from more recent studies (pooled adjusted relative risk, 7.9; 95% CI, 7.1 to 8.7). The risk of oral cancer increases in a dose-response manner with the daily number of quids consumed and the number of years chewing. In the Indian subcontinent and in Taiwan, approximately half of oral cancers reported are attributed to betel quid chewing (population attributable fraction, 53.7% for residents in Taiwan and 49.5% for the Indian population), a disease burden that could be prevented. Oral leukoplakia and oral submucous fibrosis are 2 main oral potentially malignant disorders caused by areca nut chewing that can progress to oral cancer with continued use. Ex-chewers seem to demonstrate lower risks than current chewers, but the impact of areca nut cessation on oral cancer risk has not been scientifically evaluated on the basis of randomized controlled studies. These data strongly reconfirm that betel quid chewing, primarily areca nut use, should be taken into account in assessing the cancer risk of South Asian, East Asian populations and Pacific Islanders for the development of oral cancer. [ABSTRACT FROM AUTHOR]

Areca nut and slaked lime, with or without tobacco wrapped in Piper betle leaf, prepared as betel quid, is extensively consumed as a masticatory product in many countries across the world. Betel Quid can promote the malignant transformation of oral lesions as well as trigger benign cellular and molecular changes. In the oral cavity, it causes changes at the compositional level in oral microbiota called dysbiosis. This dysbiosis may play an important role in Oral Cancer in betel quid chewers. The abnormal presence and increase of bacteria Fusobacterium nucleatum, Capnocytophaga gingivalis, Prevotella melaninogenica, Peptostreptococcus sp., Porphyromonas gingivalis, and Streptococcus mitis in saliva and/or other oral sites of the cancer patients has attracted frequent attention for its association with oral cancer development. In the present review, the authors have analysed the literature reports to revisit the oncogenic potential of betel quid and oral microbiome alterations, evaluating the potential of oral microbiota both as a driver and biomarker of oral cancer. The authors have also shared a perspective that the restoration of local microbiota can become a potentially therapeutic or prophylactic strategy for the delay or reversal of lip and oral cavity cancers, especially in high-risk population groups.

Simple Summary: This is the first study using psychometrics to investigate the association of the DSM-5 betel-quid (BQ)-related symptoms, pathological behaviors, and BQ use disorder (BUD) severity with the risk of oral squamous cell carcinoma (OSCC). This study presents data demonstrating that the symptoms of unsuccessful cutdown of BQ consumption, neglecting major roles, social or interpersonal problems, abandoning or limiting activities, hazardous use, and continued use despite awareness of the dangers were associated with the risk of OSCC. Pathological behavior of risky BQ use enhanced OSCC risk in chewers with moderate-to-severe BUD. BQ chewing is a major risk factor for oral cavity cancers; however, the risk can be mitigated by reducing pathological use. Our study indicates that targeting BUD and establishing a BUD-based strategy is a promising new direction for the prevention of OSCC. The neuroactive alkaloids in betel quid (BQ) can induce BQ addiction. We conducted a case–control study to investigate the effects of BQ-associated DSM-5 symptoms, pathological behaviors, and BQ use disorder (BUD) on oral squamous cell carcinoma (OSCC) risk. A total of 233 patients with newly diagnosed and histopathologically confirmed OSCC and 301 sex- and age-matched controls were included. BQ-related DSM-5 symptoms in the 12 months prior to disease onset were used to measure psychiatric characteristics and BUD. Compared with nonchewers, chewers with the symptoms of unsuccessful cutdown of BQ consumption, neglecting major roles, social or interpersonal problems, abandoning or limiting activities, hazardous use, and continued use despite the awareness of the dangers had a 54.8-, 49.3-, 49.9-, 40.4-, 86.2-, and 42.9-fold higher risk of developing OSCC, respectively. Mild-to-moderate and severe BUD were, respectively, associated with a 8.2–8.5- and 42.3-fold higher OSCC risk, compared with BQ nonuse. Risky BQ use of pathological behavior was associated with a 12.5-fold higher OSCC risk in chewers with no BUD or mild BUD and a 65.0-fold higher risk in chewers with moderate-to-severe BUD (p for risk heterogeneity between the two BUD groups, 0.041). In conclusion, BQ-associated DSM-5 symptoms, pathological behaviors, and BUD severity are associated with the impact of BQ chewing on OSCC development. The pathological behavior of risky BQ use enhances OSCC risk in chewers with moderate-to-severe BUD. Preventing BUD in new BQ users and treating BUD in chewers who already have the disorder are two priorities in areas where BQ chewing is prevalent. [ABSTRACT FROM AUTHOR]

Background/Aim: Programmed cell death 6 (PDCD6) is up-regulated and highly expressed in early apoptotic cells. In several types of cancer, such as cervical, breast and lung cancers, the association of PDCD6 genotypes have been investigated. However, the contribution of PDCD6 variant genotypes to oral cancer has never been examined. The current study aimed to evaluate the contribution of the PDCD6 rs4957014 and rs3756712 genotypes to the risk of oral cancer in Taiwan. Patients and Methods: The contribution of PDCD6 genotypes to oral cancer risk was examined among 958 patients with lung cancer and 958 ageand sex-matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP). Results: The data showed that the hetero-variant GT and homo-variant GG genotypes of PDCD6 rs4957014 were [ABSTRACT FROM AUTHOR]

Purpose: The aim of this cross-sectional analytical study was to evaluate the impact of smokeless tobacco (SLT) products' consumption on women's health in the selected rural areas. Methods: It was a cross-sectional rural-field area-based study in which randomly selected 500 women were asked to participate, out of which 205 women (who have completed 27 years of age with two pregnancies in life time) were selected and given a self-administered pretested in propria persona questionnaire using an objective sampling technique in 3 months. Statistical Package for the Social Sciences version-22 was used to analyze the data presented in a graphical and tabular format. Results: Among the 205 respondents, majority (73.17%) were homemakers, while 26.35% were service holders. According to the findings, SLT with betel quid has been used by 52.6% of rural women for more than 5 years. In addition, during the past 5 years, 36.6%, 48.4%, and 38.8% of SLT used tobacco zarda, plain tobacco, and khaini. 40% of the respondents said that they use SLT for the pleasure of it. There was a significant association between occupation and regular use of SLT (P < 0.05). Conclusion: Finally, despite the severe effects and consequences of using SLT, the general people, particularly women in rural areas, are unaware of its negative consequences, and its use remains unrestricted today, which is unfortunate. Approximately 63% of users were homemakers, according to this cross-sectional survey. To limit the use of SLT, a very robust comprehensive monitoring and evaluation system must be implemented at both national and international levels. Finally, it was discovered that rural women predominantly use SLT made from betel leaves, which is hazardous to both general and oral health.

Oral submucous fibrosis (OSF) is a potentially malignant condition of the oral cavity characterized by progressive fibrosis of the submucosal tissues. OSF is typically associated with the use of betel quid (BQ), a chewing package made of natural products (e.g., areca nut, betel leaves), with or without smokeless tobacco. BQ ingredients contain pro-carcinogenic bioactive compounds, but also potentially protective biomolecules, and we have shown recently that the chemical properties of different BQ recipes vary, which may explain the unequal prevalence of OSF and oral cancer in BQ users in different geographical regions. Hence, this scoping review was aimed at evaluating the existing literature regarding different BQ compounds and their association with OSF. The repository of the National Library of Medicine (MEDLINE/PubMed), medRxiv databases, Google scholar, Baidu scholar, CNKI, and EBSCO were used to search for publications that investigated the association between BQ chewing and OSF up to November 2021. The search terminology was constructed using the keywords "betel quid" and "oral submucous fibrosis", and their associated terms, with the use of Boolean operators. The search was conducted under Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, together with clear inclusion and exclusion criteria. The review showed that the risk of developing OSF varied between different BQ recipes, and that chewing BQ mixtures containing betel inflorescence (BI) significantly increased the risk of OSF, as did the addition of tobacco. Conversely, the use of betel leaf in the mixture was likely to be protective, which may be due to the presence of polyphenols. Although further research is needed to determine the effect of individual BQ ingredients in the development of OSF, our pilot results provide the scope and rationale for informing future chemopreventive strategies for OSF and oral cancer in BQ chewers. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate brain spontaneous neural activity changes in betel quid dependence (BQD) chewers using the percent amplitude of fluctuation (PerAF) method. Methods: This study included 48 BQD chewers. The healthy control (HC) group comprised 35 volunteers who were matched with BQD chewers in age, gender, and educational status. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological tests. The PerAF method was used to identify BQD-related regional brain activity changes. An independent samples t -test was used to evaluate the PerAF difference across two groups. The association between PerAF changes and clinical features such as BQD scores, duration of BQD, Hamilton Depression Rating Scale-24 item (HAMD-24), and Hamilton Anxiety Rating Scale-14 item (HAMA-14) was evaluated by using Spearman's correlation analysis. It assessed the ability of the PerAF method to distinguish between BQD chewers and HCs using a receiver operating characteristic (ROC) curve. Results: Compared to the control group, BQD chewers showed decreased PerAF in right anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), right insula, right precuneus, left putamen, left supramarginal gyrus (SMG), and left cerebellum and increased PerAF in right orbitofrontal and left superior temporal gyrus (STG) [ P < 0.05, Gaussian random field (GRF) corrected]. PerAF values of the right MFG and right ACC had a significant negative relationship with the duration of BQD (P < 0.05). The average values of PerAF in the left putamen, left cerebellum, and left STG showed significant discriminatory power in distinguishing BQD chewers from HCs, with relatively prime area under the curve (AUC) values. Conclusion: Our findings suggested that betel quid chewing is associated with spontaneous neural activity alterations in the impulsivity areas (MFG and ACC), cognitive (MFG, ACC, precuneus, and the cerebellum), and reward (orbitofrontal, putamen, and insula) systems, which may be correlated with neuropathological mechanisms of BQD. Also, PerAF may be useful as a potential sensitive biomarker for identifying spontaneous brain activity changes in BQD chewers. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to investigate brain spontaneous neural activity changes in betel quid dependence (BQD) chewers using the percent amplitude of fluctuation (PerAF) method.MethodsThis study included 48 BQD chewers. The healthy control (HC) group comprised 35 volunteers who were matched with BQD chewers in age, gender, and educational status. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological tests. The PerAF method was used to identify BQD-related regional brain activity changes. An independent samples t-test was used to evaluate the PerAF difference across two groups. The association between PerAF changes and clinical features such as BQD scores, duration of BQD, Hamilton Depression Rating Scale-24 item (HAMD-24), and Hamilton Anxiety Rating Scale-14 item (HAMA-14) was evaluated by using Spearman's correlation analysis. It assessed the ability of the PerAF method to distinguish between BQD chewers and HCs using a receiver operating characteristic (ROC) curve.ResultsCompared to the control group, BQD chewers showed decreased PerAF in right anterior cingulate cortex (ACC), right middle frontal gyrus (MFG), right insula, right precuneus, left putamen, left supramarginal gyrus (SMG), and left cerebellum and increased PerAF in right orbitofrontal and left superior temporal gyrus (STG) [P < 0.05, Gaussian random field (GRF) corrected]. PerAF values of the right MFG and right ACC had a significant negative relationship with the duration of BQD (P < 0.05). The average values of PerAF in the left putamen, left cerebellum, and left STG showed significant discriminatory power in distinguishing BQD chewers from HCs, with relatively prime area under the curve (AUC) values.ConclusionOur findings suggested that betel quid chewing is associated with spontaneous neural activity alterations in the impulsivity areas (MFG and ACC), cognitive (MFG, ACC, precuneus, and the cerebellum), and reward (orbitofrontal, putamen, and insula) systems, which may be correlated with neuropathological mechanisms of BQD. Also, PerAF may be useful as a potential sensitive biomarker for identifying spontaneous brain activity changes in BQD chewers.

The physical and chemical properties of various constitutional ingredients of betel quid (BQ) are well known in the literature. However, BQ as a whole has been rarely investigated for identifying its physical properties that can impact and modulate the disease progression of various pathologies, mainly oral submucous fibrosis (OSMF). It is quite conceivable that in the oral cavity environment, the amalgamated BQ might absorb saliva by virtue of its hygroscopic properties. As a proof of concept, we developed a methodology to quantify the hygroscopicity of the 'whole BQ' when it is mixed with saliva. To the best of our knowledge, this is the first study to report and quantify the hygroscopicity of BQ when mixed with saliva, and this forms a proof of concept for future implications in the pathogenesis of various pathologies. [ABSTRACT FROM AUTHOR]

BackgroundBetel quid chewing is associated with metabolic disorders, oral cancer, cardiovascular disease, and chronic liver diseases. Metabolic syndrome (MetS) is also a factor associated with liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, studies on the relationship between betel quid and liver fibrosis while also considering MetS are lacking. The aim of this study was thus to investigate the association of betel quid chewing and liver fibrosis with MetS.MethodsA total of 9,221 subjects were enrolled after excluding subjects