Maternal betel quid use during pregnancy and child growth: a cohort study from rural Bangladesh.

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.

Main findings: In this cohort study, no association was observed between maternal betel quid use during pregnancy and children's growth around five years of age.Added knowledge: Although catch-up growth among those born to heavy users may have attenuated any negative impact of prenatal exposure to betel quid on postnatal growth, such catch-up growth often involves greater acquisition and a more centralized distribution of body fat and insulin resistance later in life; leading to a potential heightening of cardiometabolic risk.Global health impact for policy and action: Given that betel quid consumption during pregnancy remains socially acceptable across south and south-east Asia, this study highlights the need for following up those born to betel quid users beyond childhood for capturing long-term health implications of prenatal betel quid exposure.

The association between betel quid use and oral potentially malignant and malignant disorders in Southeast Asian and Pacific regions: a systematic review and meta-analysis with GRADE evidence profile.

Background: Betel 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). Objective: We 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. Methods: This 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. Results: Nine 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. Discussion: A 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. Conclusion: The 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 Registration: PROSPERO (CRD42023429694).

Oropharyngeal stenosis in patient with oral submucous fibrosis: a case report with 8-year follow-up.

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.

Areca nut and oral cancer.

INTRODUCTION: The association between areca nut consumption and oral cancer has been a subject of increasing concern in global public health. GLOBAL PERSPECTIVE: 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. PUBLIC HEALTH: 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. CONCLUSION: 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.

Association between habitual betel quid chewing and risk of adverse cardiovascular outcomes: A systematic review.

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.

Impact of LINC00312 gene polymorphism coupled with habitual risks on buccal mucosa cancer.

Oral squamous cell carcinoma (OSCC) is a prevalent and lethal malignancy with a diverse etiology. LINC00312 is a long intergenic non-coding RNA that functions as a signal hub to regulate the progression and treatment of head and neck cancer. The aim of this study was to evaluate the effect of LINC00312 single nucleotide polymorphisms (SNPs) on the development of oral cancer. Two LINC00312 SNPs, namely rs12497104 and rs164966, were investigated among 469 male patients with cancer of buccal mucosa and 1194 gender- and age-matched controls. No significant correlation was observed between these two SNPs and the occurrence of OSCC in the case and control groups. While assessing the clinicopathological features, carriers of at least one minor allele of rs164966 (GA and GG) were less prone to develop lymph node metastasis (adjusted odds ratio [AOR], 0.666; 95% confidence interval [CI], 0.447-0.991; p=0.045) in comparison with homozygous carriers of the major allele (AA). Subsequent stratifying surveys revealed that this genetic association with nodal spread was seen only in cases who habitually chewed betel quid (AOR, 0.616; 95% CI, 0.386-0.985; p=0.042) or smoked cigarettes (AOR, 0.612; 95% CI, 0.393-0.953; p=0.029), but undetected in cases free of these main behavioral risks. Our results indicate an interactivity of LINC00312 rs164966 with lifestyle-related risks on modulating OSCC progression.

Transoral Robotic Surgery for Oral Cancer: Evaluating Surgical Outcomes in the Presence of Trismus.

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.

A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

What Motivates Betel Quid Chewers to Quit? An Analysis of Several Cessation-Relevant Variables.

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.

Association between Single Nucleotide Polymorphisms in Monoamine Oxidase and the Severity of Addiction to Betel Quid.

Betel quid (BQ) is the fourth most popular psychoactive substance in the world, and BQ use disorder (BUD) is prevalent in Asian countries. Although the mechanisms underlying BUD remain unclear, studies have reported influences from monoamine oxidase inhibitor. We enrolled 50 patients with BUD and assessed their BQ consumption habits, emotional conditions, and the clinical severity of addiction-assessed using the Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition] (DSM-5) criteria, Substance Use Severity Rating Scale, and Yale-Brown Obsessive Compulsive Disorder Rating Scale for BQ. Patients were categorized into the severe group when showing six or more symptoms defined by DSM-5. A genome-wide association study was conducted for single nucleotide polymorphisms in BRCA1, COL9A1, NOTCH1, HSPA13, FAT1, and MAOA by using patients' blood samples. More severe BUD symptoms were associated with younger age of using BQ and poor oral hygiene and with severe craving for and more anxiety toward BQ use. The MAOA rs5953210 polymorphism was significantly associated with severe BUD (odds ratio, 6.43; 95% confidence interval, 5.12-7.74; p < 0.01) and might contribute to BQ-associated cancer risk. Further studies are required to investigate the addictive properties of BQ and the development of novel diagnostic tools and pharmacotherapeutic alternatives to BUD treatment.

Facilitator experiences and lessons learned from the Betel nut intervention trial (BENIT).

BACKGROUND: The Betel Nut Intervention Trial (BENIT; ClinicalTrials.gov - NCT02942745) is the first known randomized intervention trial specifically designed for areca nut chewers in the western Pacific region who want to quit. The current study is a separate, exploratory study that examined the experiences of the BENIT facilitators during its implementation in Guam and Saipan of the Northern Mariana Islands and the extent to which the BENIT protocol was adapted to meet the participants' and facilitators' needs. METHODS: All six BENIT program facilitators completed an online survey consisting of quantitative (Likert scale) and qualitative (open-ended) questions. Survey items were grouped as follows: facilitator demographics, prior training and preparation, BENIT experience, beliefs about the program's effectiveness, and beliefs about protocol adaptations. RESULTS: Most of the facilitators felt prepared to deliver the BENIT program after several weeks of moderately intensive training. Facilitators felt the BENIT program was generally effective and that the "trigger logs" and "self-monitoring logs" worked as intended. However, they also noted that more time and support would have been helpful to overcome some of the obstacles inherent to implementing a novel program. CONCLUSION: The current findings can be used to inform, modify, and tailor subsequent areca nut cessation programs in Micronesian communities and to improve future versions of BENIT.

Duration and frequency of betel quid chewing affects periodontitis severity and life quality of people in Tanini Village, Kupang, Indonesia.

BACKGROUND: Chewing betel nuts can increase the risk of periodontal disease severity and potentially become malignant in the oral cavity. OBJECTIVE: This study aimed to investigate the effect of the duration and frequency of betel quid chewing behaviour on periodontitis severity and the life quality of people in Tanini Village, Kupang Regency, Indonesia. METHODS: The type of this study was an analytic observational study with a cross-sectional design. We used a questionnaire to obtain sociodemographic data. Oral Health Survey Basic Methods were used to measure debris index, plaque index, bleeding on probing, loss of attachment, and pocket depth. Behaviour and quality of life were measured by questionnaire and WHOQOL-BREF method as well. RESULTS: The largest number of respondents were male. Duration of chewing had a significant relationship with the frequency of chewing and periodontal status. Periodontitis was higher compared to all categories. The lifestyle of the community greatly influenced their behaviour in betel nut chewing and also affected the severity of their periodontitis and OHIs significantly. CONCLUSION: The lifestyle of betel nut chewing of the people in Tanini Village, greatly influences their behaviour. Prolonged and excessive use of betel nut induced significant adverse effects on human health. The longer and more often chew betel or areca nut, the higher the incidence of periodontitis, which significantly affects the quality of life as there is a possibility of the development of carcinogenesis, particularly in the oral cavity.

Instruments to Measure Betel Quid Dependency among Young and Adult Chewers - A Systematic Review with Meta-analysis.

Background: Betel quid (BQ) consumption is prevalent globally, majorly consumed in South-Asia and South-East Asian countries. Among the other country studies done on BQ, the focus has been on its consumption prevalence, its physiological and psychological effects, and aids to discontinue this habit. Systematic literature research on suitability of different instruments (metric or scale) to measure BQ dependency is scarce, hence pointing to the need of more evidence-based studies in this domain. Aim: The aim of the article was to identify the instruments used in the published literature to measure BQ dependency among young and adult chewers and draw a comparison. Methodology: The electronic retrieval systems and databases PubMed (Medline), Cochrane Library, Scopus, Web of Science, and Google Scholar were searched independently by two authors from January 2011 to September 2022 for the collection of desired data. Results: Among 1271 articles, 337 were duplicates and removed, 866 did not meet selection criteria. Out of 68 articles, 57 were excluded due to the lack of relevant data. Finally, only 11 articles were included for the analysis in this systematic review. Conclusion: Due to a scarcity of researches in this direction, no scale can be assigned as the best Dependence Scale, thus necessitating more such systematic reviews and meta-analysis for better comprehension and usage of present dependence scales.

The Association between Betel Quid Chewing and Metabolic Syndrome Among Urban Adults in Mandalay District of Myanmar.

Background: As the prevalence of metabolic syndrome, obesity and diabetes increase worldwide, the need to identify modifiable lifestyle risk factors also increases, especially those that may be relatively unique to a specific population. To explore a possible association between betel quid chewing and metabolic syndrome, a community-based cross-sectional study was conducted. Methodology: Three hundred ninety-one (391) adults were interviewed and the following parameters were measured: triglycerides, HDL-cholesterol, glucose, waist circumference, body mass index and blood pressure. Multiple logistic regression was used to determine the association between betel quid chewing and metabolic syndrome while controlling for confounders. Results: The prevalence of metabolic syndrome was similar in chewers and non-chewers, 50% and 49%, respectively. After controlling for other factors, development of metabolic syndrome was positively associated with number of betel quids chewed per day, age greater than 40 years, and a positive family history of hypertension and diabetes. Regarding the duration of betel chewing, when analyzed by sex, the risk was doubled in men compared to non-chewers (OR 2.15; 95% CI = 1.21, 3.84). As a result, a man chewing more than 10 pieces (OR 2.49; 95% CI = 1.36, 4.57) of betel quids per day for more than 10 years had a two-fold increased chance of developing the metabolic syndrome. Conclusions: Frequency and duration of betel quid chewing may represent a behavioral lifestyle target for approaches to reduce the incidence of metabolic syndrome.

Elemental Composition of Betel Leaves Using a Novel Optical Spectroscopic Technique.

Objective: Assess trace elements in betel leaves and slaked lime from different regions of Karnataka, India using Laser Induced Breakdown Spectroscopy (LIBS). Materials and Method: Betel leaves from six different regions of Karnataka were obtained and named (for the purpose of the study) BL1, BL2, BL3, BL4, BL5, and BL6 and they were sun-dried. A single tube of slaked lime was obtained from the local 'paan' shop. Each dried leaf and a single blob of slaked lime was subjected to elemental analysis using Laser-induced breakdown spectroscopy. Results: A ten-trial experiment was carried out in all six leaves and a blob of the slaked lime. The National Institute of Standards and Technology (NIST) database was used to assess the emission lines. The elements that were predominantly present in all six betel leaves from different regions of Karnataka are calcium, copper, and iron. Slaked lime showed only the presence of calcium. Conclusion: It is widely accepted that the consumption of betel quid causes various changes in the oral mucosa including oral potentially malignant disorders (OPMDs) and oral cancer. It is important to analyze each component of betel quid to understand the disease progression. Copper is found to be relatively higher in betel leaves, and it is known that copper-induced fibrogenesis via the lysyl oxidase pathway in oral submucous fibrosis.

Executive function deficit in betel quid-dependence: Evidence from functional and effective connectivity of executive control network.

Betel quid (BQ) ranks fourth in global self-administered psychoactive agents, after caffeine, alcohol and nicotine, with 600 million consumers. Patients with BQ dependence (BQD) disorder demonstrate deficits in executive function. However, the neural correlates of the resting-state executive control network (ECN) and BQD-related pathopsychological characteristics still remain unclear. The present study aimed to assess the functional and effective connectivity of the ECN using resting-state functional magnetic resonance imaging (rs-fMRI). Fifty-five BQD individuals and 54 healthy controls (HCs) were recruited in this study. The executive function of all participants was tested by three tasks. Independent component and Granger causal analysis were employed to investigate the functional connectivity within ECN and ECN-related directional effective connectivity, separately. Behavioural results suggested a marked deficit of executive function in BQD individuals. Compared with HCs, BQD individuals showed overall weaker functional connectivity in the ECN, mainly including dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (IPL) and middle frontal gyrus (MFG). We observed decreased outflow of information from the right DLPFC and IPL to the precentral/pre-supplement motor area (SMA) and increased outflow of information from the MFG to the middle occipital gyrus in BQD individuals. Correlation analysis revealed that the effective connectivity from IPL to precentral/pre-SMA was negatively correlated to the BQD scales in BQD individuals. Our findings revealed impaired executive function, functional connectivity of the ECN and causal interaction between networks in patients with BQD. These results could potentially direct future targets for the prevention and intervention of BQD.

Aversive Reaction Between Disulfiram and Betel Quid Among Inpatients With Alcohol Use Disorder in Bhutan: A Preliminary Study.

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.

Organic Acids Derived from Saliva-amalgamated Betel Quid Filtrate Are Predicted as a Ten-eleven Translocation-2 Inhibitor.

There is a lack of evidence regarding the use of betel quid (BQ) and its potential contribution to oral cancer. Limited attention has been directed towards investigating the involvement of BQ-derived organic acids in the modulation of metabolic-epigenomic pathways associated with oral cancer initiation and progression. We employed novel protocol for preparing saliva-amalgamated BQ filtrate (SABFI) that mimics the oral cavity environment. SABFI and saliva control were further purified by an in-house developed vertical tube gel electrophoresis tool. The purified SABFI was then subjected to liquid chromatography-high resolution mass spectrometry analysis to identify the presence of organic acids. Profiling of SABFI showed a pool of prominent organic acids such as citric acid. malic acid, fumaric acid, 2-methylcitric acid, 2-hydroxyglutarate, cis-aconitic acid, succinic acid, 2-hydroxyglutaric acid lactone, tartaric acid and ß-ketoglutaric acid. SABFI showed anti-proliferative and early apoptosis effects in oral cancer cells. Molecular docking and molecular dynamics simulations predicted that SABFI-derived organic acids as potential inhibitors of the epigenetic demethylase enzyme, Ten-Eleven Translocation-2 (TET2). By binding to the active site of α-ketoglutarate, a known substrate of TET2, these organic acids are likely to act as competitive inhibitors. This study reports a novel approach to study SABFI-derived organic acids that could mimic the chemical composition of BQ in the oral cavity. These SABFI-derived organic acids projected as inhibitors of TET2 and could be explored for their role oral cancer.

Dynamic functional connectivity changes associated with decreased memory performance in betel quid dependence.

The temporal variability of the dynamic functional connectivity (dFC) has been suggested as a useful metric for studying abnormal cognitive function. This study aimed to explore the associations between the temporal properties of dFC and memory performance in betel quid dependence (BQD). Sixty-four BQD individuals and 47 gender- and age-matched healthy controls (HCs) underwent functional magnetic resonance imaging and a series of neuropsychological assessments. The dFC was constructed by calculating the Pearson correlation coefficients within a sliding window and was clustered into three functional connectivity states using k-means clustering. The dFC temporal properties derived from the cluster results were compared between the BQD and HC groups. The results showed that States 1 and 3 featured more frequent and weak connectivity, and State 2 featured less frequent and strong connectivity. There were significant differences for mean dwell time (MDT) in State 3 (p = 0.022) and fraction of time in State 2 (p = 0.018) between the BQD and HC groups. Pearson correlation analyses showed that the MDT in State 1 was negatively correlated with long delay free recall and short delay free recall, and the MDT in State 3 was positively correlated with false positive of long delay recall. Our findings provide strong evidence that MDT match the memory performance and suggest new insights into the pathophysiological mechanism of memory disorders in BQD individuals.

The Betel Nut Intervention Trial (BENIT)-A Randomized Clinical Trial for Areca Nut and Betel Quid Cessation: Primary Outcomes.

BACKGROUND: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials-NCT02942745) is the first known randomized trial designed for ANBQ chewers. METHODS: We compared the intensive behavioral treatment intervention condition (IC) with the control condition (CC) in the BENIT and included a 5-stage early stopping rule. We report the primary analysis at stage 3. English-literate adults in Guam and Saipan who self-identified as ANBQ chewers with tobacco were enrolled between August 2016 and August 2020. IC participants (n = 88) received five in-person sessions over 22 days and a brochure containing quitting advice. CC participants (n = 88) received only the brochure. Participants were assessed at baseline and on day 22 of follow-up. Self-reported chewing status at day 22 was determined by a composite of two survey items with disparate wording and response options for cross-verification. RESULTS: Cessation rates were 38.6% (IC) and 9.1% (CC). Proportional hazards regression revealed a p = 0.0058, which met the Stage 3 criteria for significance, and an estimated reduction in ANBQ chewing for IC compared to the CC of 71% (95% CI: 41%-88%). CONCLUSIONS: Robust self-reported intervention effects at day 22 suggest that intensive cessation programs such as BENIT should be further developed and implemented on a larger scale.