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A betel quid (BQ) chewing habit has been strongly associated with the development of several oral mucosal diseases. In order to investigate whether individual components of BQ mixtures have distinct physio-pathological effects on oral mucosal cells, we examined the impact of areca nut (AN), Piper betle leaf (Leaf), Piper betle stem inflorescence (SI), areca husk (Husk) and the complete BQ mixture on the growth of oral keratinocytes (OKF-6) and primary oral fibroblasts (MMF-1). Based on their known chemical properties, we selected BQ samples from Banda Aceh (BA) and West Papua (WP) regions for our in vitro study. We used a fluorescein diacetate assay (FDA) to assess the cell viability of BQ components on OKF-6 and MMF-1 cells. The cytotoxic effect of WP-AN on the OKF-6 cell line was observed at a concentration of 100 μg/mL, resulting in a 50% reduction in cell viability (IC50) after a 2-day incubation. Similarly, BA-AN exhibited cytotoxic effect, although at a higher concentration (500 μg/mL). WP-SI also displayed cytotoxic effects at a concentration of 500 μg/mL following 2 days of incubation. In contrast, Leaf, BQ mixture and husk extracts did not show any cytotoxic effects even after 3 days of incubation. No cytotoxic effects were observed at any concentration of BQ components when exposed to MMF-1 cells. Regarding cell proliferation, MMF-1 cells exposed to BA-AN and WP-AN showed increased growth on day 1, followed by decreased growth on day 2, in a dose- and time-dependent manner. Overall, our study indicates that BQ components induce distinctive cytotoxic effects on stromal and epithelial cells from the oral cavity. [ABSTRACT FROM AUTHOR]

This study aims to determine the characterization of alluvial soil as a place to grow Chinese betel (peperomia pellucida L.) in Ambon city. Parameters studied included morphological characterization of alluvial soil and description of Chinese betel nut (Peperomia pellucid a L.). The results of observations in the field and analysis of soil samples in the laboratory that have been collected are used as material to identify soil morphological characterization. Meanwhile Chinese betel nut (Peperomia pellucid a L.) collected from alluvial soil was selectively explored by exploring the research area using the Cruise Method. Furthermore, a phytochemical test was carried out to determine its phytochemical content. The results showed that the color of the soil and the rusty color of the alluvial soil in Ambon City was generally brown. The alluvial soil structure at the study site has an O horizon with a soil layer thickness of 17 cm, an A horizon with a thickness of 45 cm soil lumpy structure and a Bw horizon with a soil thickness of 30 cm and the C horizon with a thickness of 65 cm is classified as having a globular lumpy soil structure, It has a high clay and silt content. The lower the soil solum, the lower the C-organic content. The soil in Ambon city has moderate fertility. Low base saturation is associated with low C-organic content in the soil. Chinese sirih that grows on alluvial soil types in Ambon City contains several classes of compounds that are beneficial to health like flavonoids, alkaloids, tripenoids, phenolics, tannins and saponins so that they have ethnomedicin effects such as anticancer, antimicrobial, antidiabetic, antihypertensive and antioxidant activities. [ABSTRACT FROM AUTHOR]

Background: Oral submucous fibrosis (OSF) has been reported frequently in India and other countries in South Asia. There are few reports on the clinicopathological features of OSF in China, where OSF is an epidemic. This study analyses the clinicopathological features of OSF in Hunan Province, China.Methods: A total of 674 cases of OSF were collected from July 2013 to August 2018 in Xiangya Stomatological Hospital, Central South University, and gender, age, site, pathological stage, habits, symptoms and associated lesions were recorded.Results: The male to female ratio was 32.7:1. The average age was 35.23 ± 10.08. The buccal mucosa was the most common site. A total of 99.85% of OSF cases chewed areca nut. Pale mucosa, restricted mouth opening, burning and fibrous bands were common clinical manifestations. Oral leukoplakia (OLK) was the most common associated lesion. The extended duration of chewing areca nut increased the risk of associated lesions (P < 0.05). The risk of OSF associated with OLK decreased with increasing OSF stage (P < 0.05).Conclusion: The prevalence of OSF in males was higher than that in females, the buccal mucosa was most affected, and chewing areca nut is the most common habit of OSF patients. [ABSTRACT FROM AUTHOR]

Background: The handling and disposal of municipal solid waste is becoming a natural and a general well-being concern. An alarming increase in the morbidity and mortality from respiratory diseases is due to the exposure of the sanitary workers, to the contamination of atmospheric oxygen that is ambient and particulate. Due to their introduction to numerous hazard factors, they endure high rates of occupational medical issues. In the total populations about 10% of them having the habit of betel quid chewing. Areca nut is the seed of the palm tree Areca catechu, which is the fourth most commonly used psychoactive substance, next to caffeine, nicotine, and alcohol. The recent investigations propose that the usage of betel nut remains as a major cause for the onset of such systemic diseases as metabolic and cardiorespiratory ailments. Aim: This study was aimed to understand the effects of betel chewing which, in turn, causes cardiovascular and respiratory changes on sanitary workers of Kanchipuram municipality. Materials and Methods: It is a comparative study analysis, in which nearly 100 sanitary workers actively participated and the following data were obtained based on blood pressure and pulse using sphygmomanometer. Mean arterial pressure and pulse pressure were also calculated from the anthropometry measurements measured using height and weight machine. The pulmonary function test was obtained using computerized spirometer - HELIOS 701. The sanitary workers were divided into two groups such as 50 betel chewing sanitary workers (Group 1) and 50 non-betel chewing sanitary workers (Group-2). Pulmonary test parameters such as forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), peak expiratory flow rate (PEFR), FEV1 to FVC, PEFR (FEFR25-75), and respiratory endurances were compared with the two groups and the results were obtained. Results: On comparing the cardiovascular and respiratory parameters of the sanitary workers, the result showed many significant changes between the non-betel groups and betel chewing sanitary workers. Conclusion: The findings of our study clearly showed that both betel and non-betel chewing sanitary workers have cardiopulmonary alteration, but betel chewing sanitary workers have mild reduction with cardiopulmonary parameters than non-betel chewing sanitary workers. [ABSTRACT FROM AUTHOR]

The psychoactive effects of using areca nut and its potential for dependence have been observed. However, the factors that create barriers to or promote chewing cessation are not well understood. This study aims to explore the behavioral changes of betel quid chewers who have been diagnosed with oral cancer within a transtheoretical model framework. Thirty oral cancer patients with betel quid chewing history were chosen for in-depth interviews. Qualitative content analysis was used to analyze the data and identify themes that described the behavioral changes of betel quid cessation. Our research showed that betel quid chewers with oral cancer typically experience four significant stages of behavior: pre-contemplation, contemplation, action, and maintenance. Each stage change was marked by specific characteristics. At first, chewers showed positive attitudes toward the psychoactive or social effects of betel quid. They then realized the negative effects of betel quid, such as dental or other physical problems. Some also realized that they were addicted to betel quid. When they decided to quit, most chewers reported going “cold turkey.” Some chewers successfully quit betel quid and attributed it to willpower. Those quitting because of the loss of oral functions were unable to chew anymore, though some chewers had experienced a relapse. In the maintenance stage, ex-chewers reported overcoming their addiction; however, relapse was possible. In this study, those who quit betel quid because of oral cancer usually quit tobacco and alcohol as well, with a lesser chance of recurrence. As the maintenance of chewing betel quid is multifactorial, this study provides information for betel quid cessation and oral cancer prevention. [ABSTRACT FROM AUTHOR]

Teeth are one of the key to understand disease and cultural influence in the past. This research describes abnormalities and cultural influences found in teeth belongs to Addatuang Sidenreng which is a royalty buried in Jera Lompo'E, South Sulawesi, Indonesia (17th century). The material consists of 13 teeth which currently curated in Laboratory of Bioanthropology and Paleoanthropology, UGM, Indonesia. This research uses bioarchaeological method and macroscopical analysis. The results are the individual age estimation, health status and cultural influences, such as betel chewing and dental filing which still practiced even after Islam enters Sulawesi, Indonesia. [ABSTRACT FROM AUTHOR]

Rationale TheWorld Health Organization regards betel quid (BQ) as a human carcinogen, and DSM-IVand ICD-10 dependence symptoms may develop with its heavy use. BQ's possible effects of an enhanced reward system and disrupted inhibitory control may increase the likelihood of habitual substance use. Objectives The current study aimed to employ resting-state fMRI to examine the hypothesized enhanced reward system (e.g., the basal forebrain system) and disrupted inhibitory control (e.g., the prefrontal system) in BQ chewers. Methods The current study recruited three groups of 48 male participants: 16BQ chewers, 15 tobacco- and alcohol-user controls, and 17 healthy controls. We used functional connectivity (FC), mean fractional amplitude of low-frequency fluctuations (mfALFF), and mean regional homogeneity (mReHo) to evaluate functional alternations in BQ chewers. Graph theoretical analysis (GTA) and network-based statistical (NBS) analysis were also performed to identify the functional network differences among the three groups. Results Our hypothesis was partially supported: the enhanced reward system for the BQ chewers (e.g., habitual drug-seeking behavior) was supported; however, their inhibitory control was relatively preserved. In addition, we reported that the BQ chewers may have enhanced visuospatial processing and decreased local segregation. Conclusions The current results (showing an enhanced reward system in the chewers) provided the clinicians with important insight for the future development of an effective abstinence treatment. [ABSTRACT FROM AUTHOR]

Streets and sidewalks are often read as mere targets of urban development schemes, rarely acknowledged for their importance to various forms of everyday life. Western notions of public space as designed green places of relief from urbanity, or as the imagined public plazas and agoras of civic discussions, are inadequate theoretical frames that cannot account for the sidewalk, thepaan-shop, or the tea-stall, as sites of commensality, conviviality, and potential violence. Drawing on personal experience and a range of secondary literature an alternative way of thinking about the streets and re-imagining the national cultural space is proposed —less officious, less bureaucratic, less national—than has been allowed so far in considerations of good taste. [ABSTRACT FROM PUBLISHER]

Aims: To assess the prevalence, knowledge, and attitude of gutkha chewing among school children of Arsikere, India. Materials and Methods: Two thousand school children aged between 10 and 15 years were examined with individual interviews along with a questionnaire to evaluate the presence of betel nut and paan chewing habit in various forms. Children of both sexes were included in the study. Responses of all study population and the association between dependent and explanatory variables were assessed using Chi-square test. Results: Twenty-eight percent of children had the habit of gutkha chewing, more among boys than girls at the ratio of 4:1 which was statistically significant ( P < 0.05). The habit was more common in government school children than private school children; over 70% of children believed that it is a bad habit, but half the study population was not aware of side effects; 30% of children believed that it is not a bad habit and has no side effects. Conclusion: There is a higher prevalence of gutkha chewing habit in school children who are not aware of the side effects. Children themselves purchase the gutkha and betel nut sachets, hence the Government should ban the sale and purchase by children. [ABSTRACT FROM AUTHOR]

Background: With 600 million people using betel quid (BQ) globally, and smokeless tobacco (SLT) use being more wide-spread; the duo is an uphill public health concern in South Asian countries. SLT and/or BQ use increases the risk for morbidity and mortality from oral cancer. Because SLT and/or BQ use is initiated during adolescence, it renders this group more vulnerable; and particular attention is needed to curb SLT and/or BQ use to reduce related disease burden. We aimed to observe the differential individual, social and environmental features amongst SLT and/or BQ users to determine the key influencers of its use in adolescents.Methods: This study was a cross-sectional survey of 2140 adolescents from secondary schools of Karachi, Pakistan. The main outcome measure was SLT and/or BQ use based on their consumption in the past 30 days. Univariate and multivariate regression binary logistic analyses were employed while reporting results in both crude form and adjusted odds ratio (after adjusting for all remaining individual, social and environmental level variables) with 95% confidence level. A p-value of < .05 was considered significant for all analyses.Results: The overall prevalence of SLT and/or BQ use was 42.6% (n = 912) of the total sample. The SLT and/or BQ consumer group had more males than females. A significant proportion of user (n = 558, 61.2%) was found in co-education schools. Students whose peers (OR = 6.79, 95% CI 4.67-9.87, p-value <0.001) and/or either of the parents (OR = 2.16, 95% CI 1.73-2.65, p-value <0.001) used SLT and/or BQ, alongside, adolescents who had not attended knowledge based sessions in schools regarding harmful effects of SLT and/or BQ were more likely to consume it. It's availability with outside school hawkers increased the odds of its use by 6 times, as indicated by both univariate and multivariate models after adjusting for the remaining variables.Conclusion: In conclusion, students studying in co-education, parents and peers use, lack of knowledge based sessions on harmful health effects of SLT and/or BQ, and easy availability of the product from hawkers outside school all contribute towards enhanced risk of SLT and/or BQ use in adolescents. [ABSTRACT FROM AUTHOR]

Betel quid chewing is implicated in the high prevalence of oral cancer in Southeast Asian countries. One of the major components of betel quid is arecoline. In the present study, in order to characterize the association between chronic arecoline stimulation and carcinogenesis the expression level of matrix metalloproteinase (MMP)‑2, MMP‑9, tissue inhibitor of metalloproteinase (TIMP)‑1 and TIMP‑2 mRNA in human gingival epithelial progenitor cells (HGEPs) stimulated with arecoline was assessed. The HGEPs were alternated between 3 days of incubation with arecoline (50 µg/ml), and 3 days without arecoline, for up to 30 days. The expression levels of the MMPs and TIMPs in the cells stimulated with arecoline were evaluated by reverse transcription-quantitative polymerase chain reaction at 18 and 30 days. The expression of MMP‑9 mRNA in the experimental group was significantly increased compared with in the control group (P<0.01). No significant differences in the expression of MMP‑2, TIMP‑1 or TIMP‑2 mRNA were observed between the experimental and control groups. Using an MMP‑9 activity assay, the levels of MMP‑9 activity in the experimental group were demonstrated to be significantly higher than in the control group (P<0.05). To investigate associated cellular signaling pathways, PDTC [a nuclear factor (NF)‑κB/inhibitor of NF‑κB (IκB) inhibitor], PD98059 [a mitogen-activated protein kinase kinase (MAPKK)1 and MAPKK2 inhibitor], SB203580 (a p38 MAPK inhibitor) and 5,15‑DPP [a signal transduction and activator of transcription (STAT) 3 inhibitor] were used. All inhibitors decreased the extent of MMP‑9 upregulation induced by stimulation with arecoline. Based on the data, it is hypothesized that MMP‑9 activity may be involved in the pathological alterations of oral epithelium induced by betel quid chewing, and that the NF‑κB/IκB, MAPK, p38 MAPK and STAT3 signaling pathways may be involved in the production of MMP-9 induced by betel quid chewing. [ABSTRACT FROM AUTHOR]

Background: To reduce oral cancer mortality, an organized, population-based screening program for the early detection of oral premalignancy and oral cancer was designed for high-risk individuals with habits of betel quid chewing, cigarette smoking, or both. The objective of this report was to evaluate the long-term effectiveness of this program in reducing the incidence of advanced disease and deaths from oral cancer.Methods: A nationwide, population-based screening program for oral cancer has been conducted in Taiwan since 2004. Residents aged ≥ 18 years with oral habits of cigarette smoking and/or betel quid chewing were invited. The standardized mortality ratio method was used to compare the observed numbers of advanced oral cancers and deaths from oral cancer among screening attendees with the expected numbers derived from mortality among nonattendees. An intention-to-treat analysis of the relative rate of reductions in advanced-stage oral cancers and oral cancer mortality also was conducted.Results: The overall screening rate was 55.1%. The relative risk of death from oral cancer was 0.53 (95% confidence interval [CI], 0.51-0.56) as a result of screening compared with the expected risk of oral cancer deaths in the absence of screening. The corresponding relative risk was 0.74 (95% CI, 0.72-0.77) after adjusting for self-selection bias. The relative risk of advanced oral cancer for the screened group versus the nonscreened group was 0.62 (95% CI, 0.59-0.64), which increased to 0.79 (95% CI, 0.76-0.82) after adjustment for self-selection bias.Conclusions: An organized, population-based oral cancer screening program targeting more than 2 million Taiwanese cigarette smokers and/or betel quid chewers demonstrated the effectiveness of reducing stage III or IV oral cancers and oral cancer mortality. These evidence-based findings corroborate and support the screening strategy of oral visual inspection for the prevention of oral cancer among high-risk individuals in areas with a high incidence of oral cancer. Cancer 2017;123:1597-1609. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

This study aims to describe betel quid chewing practice and compare oral potentially malignant disorders between chewers and non-chewers of betel quid among residents in Dagon Myothit (East) Township, Myanmar. The study used a cross-sectional design conducted with a representative sample of 542 adults aged 18 years and above in the township. The trained interviewers collected data using a pretested structured questionnaire. On-site oral examination was done for suspected oral lesions. The mean age of the respondents was 45 years and 59% were women. Fifty-two percent of the respondents were currently in the habit of chewing betel quids (72% of men and 39% of women). Among 284 current betel quid chewers, 240 (85%) chewed betel quids together with tobacco. Out of 284 current betel quid chewers, 24 (8.5%) were found to have oral potentially malignant disorders; out of 258 betel quid non-chewers, only 1 (0.4%) was found to have oral potentially malignant disorders. This highlights the growing importance of smokeless tobacco use as public health problem. [ABSTRACT FROM AUTHOR]

Purpose: Betel quid chewing is a major oral cancer risk factor and the human papillomaviruses (HPV) may play an aetiological role in these cancers. However, little is known about the shape of the dose-response relationship between the betel quid chewing habit and oral cancer risk in populations without HPV. We estimate the shape of this dose-response relationship, and discuss implications for prevention.Methods: Cases with oral squamous cell carcinoma (350) and non-cancer controls (371) were recruited from two major teaching hospitals in South India. Information on socio-demographic and behavioral factors was collected using a questionnaire and the life grid technique. The effect of daily amount of use and duration of the habit were estimated jointly as risk associated with cumulative exposure (chew-years). The shape of the dose-response curve was estimated using restricted cubic spline transformation of chew-years in a conditional logistic regression model. Risk estimates for low dose combinations of daily amount and duration of the habit were computed from flexible regression.Results: Most (72%) oral cancer cases were betel quid chewers in contrast to only 18% of controls. A nonlinear dose-response relationship was observed; the risk increased steeply at low doses and plateaued at high exposures to betel quid (>425 chew-years). A threefold increase in risk (OR=3.92, 95%CI: 1.87-8.21) was observed for the lowest dose; equivalent to the use of one quid per day for one year.Conclusion: Our findings may be used to counsel people to refrain from even low betel quid chewing. [ABSTRACT FROM AUTHOR]

Rational: Betel quid is regarded as a human carcinogen by the World Health Organization. It remains unknown whether chewing betel quid has a chronic effect on healthy betel quid chewers' memory. Objectives: The present study aims to investigate whether chewing betel quid can affect short-term memory (STM). Methods: Three groups of participants (24 dependent chewers, 24 non-dependent chewers, and 24 non-chewers) were invited to carry out the matrix span task, the object span task, and the digit span task. All span tasks' results were adopted to assess spatial STM, visual STM, and verbal STM, respectively. Besides, there are three set sizes (small, medium, and large) in each span task. Results: For the matrix span task, results showed that the dependent chewers had worse performances than the non-dependent chewers and the non-chewers at medium and large set sizes. For the object span task and digit span task, there were no differences in between groups. In each group, recognition performances were worse with the increasing set size and showing successful manipulation of memory load. Conclusions: The current study provided the first evidence that dependent betel quid chewing can selectively impair spatial STM rather than visual STM and verbal STM. Theoretical and practical implications of this result are discussed. [ABSTRACT FROM AUTHOR]

Background: Transgenerational effects of paternal Areca catechu nut chewing on offspring metabolic syndrome (MetS) risk in humans, on obesity and diabetes mellitus experimentally, and of paternal smoking on offspring obesity, are reported, likely attributable to genetic and epigenetic effects previously reported in betel-associated disease. We aimed to determine the effects of paternal smoking, and betel chewing, on the risks of early MetS in human offspring.Methods: The 13 179 parent-child trios identified from 238 364 Taiwanese aged ≥20 years screened at 2 community-based integrated screening sessions were tested for the effects of paternal smoking, areca nut chewing, and their duration prefatherhood on age of detecting offspring MetS at screen by using a Cox proportional hazards regression model.Results: Offspring MetS risks increased with prefatherhood paternal areca nutusage (adjusted hazard ratio, 1.77; 95% confidence interval [CI], 1.23-2.53) versus nonchewing fathers (adjusted hazard ratio, 3.28; 95% CI, 1.67-6.43) with >10 years paternal betel chewing, 1.62 (95% CI, 0.88-2.96) for 5 to 9 years, and 1.42 (95% CI, 0.80-2.54) for <5 years betel usage prefatherhood (Ptrend=0.0002), with increased risk (adjusted hazard ratio, 1.95; 95% CI, 1.26-3.04) for paternal areca nut usage from 20 to 29 years of age, versus from >30 years of age (adjusted hazard ratio,1.61; 95% CI, 0.22-11.69). MetS offspring risk for paternal smoking increased dosewise (Ptrend<0.0001) with earlier age of onset (Ptrend=0.0009), independently.Conclusions: Longer duration of paternal betel quid chewing and smoking, prefatherhood, independently predicted early occurrence of incident MetS in offspring, corroborating previously reported transgenerational effects of these habits, and supporting the need for habit-cessation program provision. [ABSTRACT FROM AUTHOR]

Betel nut is the second largest economic food product in Taiwan. In Southeast Asia, the habit of chewing betel nut seems to be highly correlated with oral submucous fibrosis and oral squamous cell carcinoma. Oral submucous fibrosis is characterized by abnormal accumulation of oral submucous collagen fibers and limitation of mouth opening. Although the mechanism responsible for tissue damage is still unknown, prolonged irritation caused by betel nut and tobacco is considered to be a major factor contributing to the pathogenesis of oral submucous fibrosis. The effect of betel nut chewing on immune system remains unknown. Present study aims to investigate the change of plasma hormones including cortisol, testosterone, and inflammatory cytokine concentrations in male chewing betel nut compared with normal subjects. Heparinized blood was obtained from control group (normal young + mid-aged individuals), betel nut-chewing, and oral cancer male subjects. The study was approved by the Ethics Committee of the Chang-Gung Memorial Hospital. Written informed consent was granted by the patients. Plasma cortisol and testosterone concentrations were detected by commercial enzyme-linked immunosorbent assay (ELISA). The inflammatory cytokines, including interleukin-1β (IL-1β), IL-15, tumor necrosis factor-α (TNF-α), were analyzed by ELISA with commercial monoclonal capture antibodies and polyclonal detection antibodies. The median concentrations of plasma IL-1β, IL-15, and TNF-α were 3.14 pg/ml, 3.14 pg/ml, and 6.85 pg/ml, respectively, in patients with oral cancer, compared with median plasma IL-1β, IL-15, and TNF-α concentration of 2.64 pg/ml, 5.86 pg/ml, and 5.38 pg/ml, respectively, in patients with betel nut-chewing habit. In contrast, the median concentrations of plasma IL-1β, IL-15, and TNF-α in mid-aged males (aged 30–50) were 7.00 pg/ml, 10.64 pg/ml, and 31.73 pg/ml, respectively, compared with median plasma concentration of IL-1β, IL-15, and TNF-α of 4.48 pg/ml, 33.36 pg/ml, and 97.77 pg/ml in young males (aged 20–22), respectively. Also, significantly elevated plasma cortisol concentration was noted in betel nut-chewing (median 727.2 ng/ml) and oral cancer patients (561.9 ng/ml) compared to the mid-aged (176.8 ng/ml) and young males (173.4 ng/ml), respectively. In addition, lower plasma testosterone concentrations were found in betel nut-chewing subjects compared with young males (2.6 ± 3.3 ng/ml vs 6.2 ± 2.9 ng/ml). To summarize, the inflammatory cytokines and steroid hormones may reflect the degree of inflammation in betel nut-chewing males and the oral cancer subjects. The above findings suggest that betel nut-chewing or oral cancer inhibits plasma cytokines and regulates steroid hormones concentrations compared to mid-aged or young normal subjects. It is also indicated that betel nut-chewing causes decreased inflammatory cytokines as the same levels as in oral cancer subjects. [ABSTRACT FROM AUTHOR]

Oral cancer is the sixth most common malignancy in the world. Oral cancer is of major concern in Southeast Asia primarily because of the prevalent oral habits of betel quid chewing, smoking, and alcohol consumption. Despite recent advances in cancer diagnoses and therapies, the 5.year survival rate of oral cancer patients has remained at a dismal 50% in the last few decades. This paper is an overview of the various etiological agents and risk factors implicated in the development of oral cancer. [ABSTRACT FROM AUTHOR]

Areca nut (AN) chewing is associated with chronic kidney disease (CKD). However, the molecular mechanisms of AN-induced CKD are not known. Thus, we studied the effects of arecoline, a major alkaloid of AN, on proximal tubule (LLC-PK1) cells in terms of cytotoxicity, fibrosis, transforming growth factor-β (TGF-β) and c-Jun N-terminal kinase (JNK). We found that arecoline dose (0.1–0.5 mM) and time (24–72 h)-dependently induced cytotoxicity without causing cell death. Arecoline (0.25 mM) also time-dependently (24–72 h) increased fibronectin and plasminogen activator inhibitor-1 (PAI1) protein expressions. Arecoline (0.25 mM) time-dependently (24–72 h) increased TGF-β gene transcriptional activity and supernatant levels of active TGF-β1. Moreover, arecoline (0.25 mM) activated JNK while SP600125 (a JNK inhibitor) attenuated arecoline-induced TGF-β gene transcriptional activity. SP600125, but not SB431542 (a TGF-β receptor type I kinase inhibitor), attenuated arecoline-induced fibronectin and PAI1 protein expressions. Finally, tubulointerstitial fibrosis occurred and renal cortical expressions of fibronectin and PAI1 proteins increased in arecoline-fed mice at 24 weeks. We concluded that arecoline induced tubulointerstitial fibrosis in mice while arecoline-induced TGF-β and pro-fibrotic proteins (fibronectin, PAI1) are dependent on JNK in LLC-PK1 cells. [ABSTRACT FROM AUTHOR]

Objective: It is generally acknowledged that drug dependence is connected with abnormal functional organization in the individual's brain. The present study aimed to identify the anterior cingulate cortex (ACC) abnormality with the cerebral networks involved in betel quid dependence (BQD) by resting-state functional connectivity (rsFC) using functional magnetic resonance imaging (fMRI).Methods: With fMRI data measured from 33 resting-state BQD individuals and 32 non-addicted and age-, sex-, education-matched healthy controls, we inquired into the BQD-related changes in FC between the regions of ACC with the whole brain involved in BQD individuals using a region of interest vised method, and to identify the relation of the alteration with the severity of BQD and duration.Results: Compared to controls, the BQD group showed increased connectivity from ACC to the regions of the reward network (brainstem including midbrain regions such as the ventral tegmental area and pons, caudate, thalamus) and cerebellum. Decreased connectivity was observed in the BQD group in regions from ACC to the default mode network (medial prefrontal cortex and precuneus) and para Hippocampal/hypothalamus. Specifically, the BQD scale was positively correlated with increased FC of right ACC to left thalamus and left ACC to pons; the durations were negatively correlated with FC of right ACC to left precuneus.Conclusion: These disturbances in rsFC from ACC to the reward network and DMN revealed by fMRI may have a key function in providing insights into the neurological pathophysiology underlying BQD-associated executive dysfunction and disinhibition. These findings may contribute to our better understanding of the mechanisms underlying BQD. [ABSTRACT FROM AUTHOR]

Betel quid chewing is associated with various oral cancers and other health concerns, including reproductive health issues. Nevertheless, the practice is widespread in Myanmar, especially among men. This qualitative study elucidates the gendered aspects of betel quid chewing by examining how it links with masculine ideology among male betel quid chewers in Mandalay, Myanmar. Data were collected through in-depth interviews, focus-group discussions, key-informant interviews and participant observation. The thematic content analysis was guided by Connell’s concept of hegemonic masculinity and Butler’s notion of gender performativity. The findings indicated that young Mandalay men were drawn to betel quid chewing by the value they gave to satisfying their curiosity, power competition, risk-taking and a display of manliness. Thus, the practice of betel quid chewing, as defined by our participants, was perceived as manly, trendy, stylish and sexually attractive. For adult men, betel quid chewing was a social lubricant that assisted them in talking with clients and co-workers, thus enhancing their economic opportunities with other men. It also helped working-class men to work harder. Betel quid chewing harm-reduction programmes therefore need to be mindful of masculinity issues as well as the economic aspects of betel quid chewing. [ABSTRACT FROM PUBLISHER]

Objectives: The expression levels of two DNA repair genes ( CHAF1A and CHAF1B) and a chromosome segregation gene ( AURKA) were susceptible to arecoline exposure, a major alkaloid of areca nut. We hypothesize that genetic variants of these genes might also be implicated in the risk of oral cancer and could be modified by substance use of betel quid or alcohol and cigarettes. Material and methods: A case-control study, which included 507 patients with oral cancer and 717 matched controls, was performed in order to evaluate the cancer susceptibility by the tagging single-nucleotide polymorphisms (tagSNPs) in AURKA, CHAF1A, and CHAF1B using a genotyping assay and gene-environment interaction analysis. Results: The Phe31Ile polymorphism (rs2273535, T91A) of AURKA was significantly associated with an increased risk of oral cancer (odds ratio (OR) = 2.1, 95 % confidence interval (CI) 1.2-3.5). The gene dosage of the 91A allele also showed a significant trend in risk of oral cancer ( P = 0.008). Furthermore, we found the AURKA 91AA homozygote was modifiable by substance use of alcohol, betel quid, and cigarettes (ABC), leading to increased risk of oral cancer in an additive or a multiplicative model (combined effect indexes = 1.2-4.0 and 1.5-2.2, respectively). However, no association was observed between the genetic variants of CHAF1A or CHAF1B and oral cancer risk in the study. Conclusion: These findings reveal the functional Phe31Ile polymorphism tagSNP of AURKA may be a strong susceptibility gene in ABC-related oral cancer occurrence. Clinical relevance: The results of this betel-related oral cancer study provide the evidence of environment-gene interaction for early prediction and molecular diagnosis. [ABSTRACT FROM AUTHOR]

Periodontitis is a polymicrobial anaerobe infection. Little is known about the dysbiotic microbiota and the role of bacterial metabolites in the disease process. It is suggested that the production of certain waste products in the proteolytic metabolism may work as markers for disease severity. Hydrogen sulfide (H 2 S) is a gas produced by degradation of proteins in the subgingival pocket. It is highly toxic and believed to have pro-inflammatory properties. We aimed to study H 2 S production from subgingival plaque samples in relation to disease severity in subjects with natural development of the disease, using a colorimetric method based on bismuth precipitation. In remote areas of northern Thailand, adults with poor oral hygiene habits and a natural development of periodontal disease were examined for their oral health status. H 2 S production was measured with the bismuth method and subgingival plaque samples were analyzed for the presence of 20 bacterial species with the checkerboard DNA–DNA hybridization technique. In total, 43 subjects were examined (age 40–60 years, mean PI 95 ± 6.6%). Fifty-six percent had moderate periodontal breakdown (CAL > 3 < 7 mm) and 35% had severe periodontal breakdown (CAL > 7 mm) on at least one site. Parvimonas micra , Filifactor alocis , Porphyromonas endodontalis and Fusobacterium nucleatum were frequently detected. H 2 S production could not be correlated to periodontal disease severity (PPD or CAL at sampled sites) or to a specific bacterial composition. Site 21 had statistically lower production of H 2 S ( p = 0.02) compared to 16 and 46. Betel nut chewers had statistically significant lower H 2 S production ( p = 0.01) than non-chewers. Rapid detection and estimation of subgingival H 2 S production capacity was easily and reliably tested by the colorimetric bismuth sulfide precipitation method. H 2 S may be a valuable clinical marker for degradation of proteins in the subgingival pocket. [ABSTRACT FROM AUTHOR]

Betel quid is a psychoactive drug preparation typically made up of a combination of areca quid, slaked lime, piper betel leaf and tobacco. It is the fourth most commonly consumed drug in the world with global use concentrated in the Asia-Pacific region (Boucher and Mannan, 2002; Warnakulasuriya and Peters, 2002). The International Agency for Research on Cancer has classified betel quid as a Group 1 carcinogen (IARC, 2004; Lin et al., 2006), and its use has been associated with oral and oropharyngeal cancer, oral lesions, oral leukoplakia, submucous fibrosis, gum disease, and cancer of the pharynx and esophagus (IARC, 2004; Oakley et al., 2005; Shah et al., 2002; Warnakulasuriya, 2002). This paper reports on the feasibility of an innovative betel quid cessation program carried on the U.S. territory of Guam, and is the first of its kind. The program is described, along with the challenges encountered during the implementation process. [ABSTRACT FROM AUTHOR]

A 65-year-old lady presented with large, asymptomatic normal coloured pedunculated growth of 3.5 centimeter in length over hard palate since last two years. Patient had a history of betel leaf and nut ingestion with other irritant agents for several decades. All hematological investigations were within normal limit but radiographic imaging revealed soft tissue shadow. After excision, histopathological examination revealed bundles of spindle cells producing extensive collagen in both radiating and circular pattern in lower dermis with focal pseudoepitheliomatous hyperplasia in mucosal epithelium and chronic inflammatory infiltrates in submucosa. All these features were consistent with irritation fibroma with unusual size. It was located in palate which was very unusual location. [ABSTRACT FROM AUTHOR]

Betel nut chewing causes cancer in humans, including strong associations with head and neck cancer in Guam. In the search for biomarkers of betel chewing we sought to identify chemicals specific for the 3 most commonly consumed betel preparations in Guam: nut (‘BN’), nut +  Piper betle leaf (‘BL’), and betel quid (‘BQ’) consisting of nut + lime + tobacco +  Piper betle leaf. Chemicals were extracted from the chewing material and saliva of subjects chewing these betel preparations. Saliva analysis involved protein precipitation with acetonitrile, dilution with formic acid followed by LCMS analysis. Baseline and chewing saliva levels were compared using t-tests and differences between groups were compared by ANOVA; p < 0.05 indicated significance. Predominant compounds in chewing material were guvacine, arecoline, guvacoline, arecaidine, chavibetol, and nicotine. In chewing saliva we found significant increases from baseline for guvacine (BN, BQ), arecoline (all groups), guvacoline (BN), arecaidine (all groups), nicotine (BQ), and chavibetol (BL, BQ), and significant differences between all groups for total areca-specific alkaloids, total tobacco-specific alkaloids and chavibetol. From this pilot study, we propose the following chemical patterns as biomarkers: areca alkaloids for BN use, areca alkaloids and chavibetol for BL use, and areca alkaloids plus chavibetol and tobacco-specific alkaloids for BQ use. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most commonly diagnosed cancer among the female population of Assam, India. Chewing of betel quid with or without tobacco is common practice among female population of this region. Moreoverthe method of preparing the betel quid is different from other parts of the country. So matched case control study is conducted to analyse whetherbetel quid chewing plays a significant role in the high incidence of breast cancer occurrences in Assam. Methods and Material: Here, controls are matched to the cases by age at diagnosis (±5 years), family income and place of residence with matching ratio 1:1. Conditional logistic regression models and odd ratios (OR) was used to draw conclusions. Results: It is observed that cases are more habituated to chewing habits than the controls. Further the conditional logistic regression analysis reveals that betel quid chewer faces 2.353 times more risk having breast cancer than the non-chewer with p value 0.0003 (95% CI 1.334-4.150). Conclusion:Though the female population in Assam usually does not smoke, the addictive habits typical to this region have equal effect on the occurrence of breast cancer. [ABSTRACT FROM AUTHOR]

Background: In this study, cardiometabolic risk associated with betel-quid, alcohol and cigarette use, based on a simple index-lipid accumulation product (LAP), was investigated in Taiwanese male factory workers. Methods: Male factory workers were recruited during their annual routine health examination at a hospital in south Taiwan. The risk of cardiometabolic disorderswas estimated by the use of LAP, calculated as (waist circumference [cm]265)x(triglyceride concentration [mmol/l]). Multiple linear regression analyses were conducted to assess the risk factors of natural logarithm-transformed LAP. Results: Of the 815 participants, 40% (325/815) were current alcohol users, 30% (248/815) were current smokers and 7% (53/815) were current betel-quid users. Current betel-quid use, alcohol use, older age, lack of exercise and higher body mass index were found to be significant and independent factors associated with natural logarithm-transformed LAP. Conclusions: Betel-quid and alcohol, but not cigarette use, were independent risk factors of logarithmtransformed LAP, adjusting for age, exercise and body mass index in male Taiwanese factory workers. LAP can be considered as a simple and useful method for screening of cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Background Besides the well-known risk factors, Epstein-Barr virus ( EBV) might play a significant role in oral squamous cell carcinoma ( OSCC). To explore the role of EBV in OSCC, the prevalence of EBV infection in oral exfoliated cells of OSCC cases and controls in northeastern Thailand was investigated, and the association of EBV in tumor lesion cells was further confirmed. Methods Oral exfoliated cells were collected from OSCC cases and non-cancer controls. Cells from tumor lesions were taken from OSCC patients for further strong confirmation of the association of EBV with OSCC. EBV DNA was detected by polymerase chain reaction ( PCR) using primers specific for EBV DNA polymerase. The EBV DNA positive samples were confirmed further by nested PCR. Results Epstein-Barr virus was detected in the oral exfoliated cells of 45.05% of OSCC patients and 18.08% of the non-cancer control ( P < 0.001). Similarly, EBV was detected in 32.5% of the tumor lesions. Betel quid chewing was statistically significantly associated with EBV prevalence ( OR = 2.08), whereas no association with tobacco smoking and alcohol consumption. Alcohol consumption and betel quid chewing were significantly associated with OSCC ( OR = 3.05 and OR = 5.05, respectively), but tobacco smoking was not associated. Interestingly, EBV was significantly associated with OSCC ( OR = 3.76). Conclusions Epstein-Barr virus prevalence is associated with OSCC and seems to be enhanced by betel quid chewing, suggesting that EBV may, together with betel quid chewing, act as an important etiological risk factor of OSCC. [ABSTRACT FROM AUTHOR]

Chewing of betel quid, smoking and alcohol consumption are all associated with higher incidences of oral cancer. Genetic damage can be detected by fluorescent in situ hybridization (FISH) using human centromeric probes. In the present study FISH was performed on buccal epithelial cells of pan masala and gutkha chewers alone with and without additional tobacco smoking and/or alcohol consumption. The study comprised of 1500 male individuals. The present study found the highest frequency of micronuclei without a centromeric region (MN−) among gutkha users who also smoked and drank (P < 0.05). A significant increase in cells having micronuclei with a centromeric region (MN+) was observed among pan masala users who also smoked (P < 0.05). The study reveals that the clastogenic effects of pan masala/gutkha increase with smoking and alcohol consumption, but aneugenic effects were also observed among the pan masala chewers who smoked. [ABSTRACT FROM PUBLISHER]

Objective: Betel quid and areca nut chewing is widely prevalent in many parts of Asia and Asian migrant communities in the world. Due to the carcinogenicity associated with quid and areca nut we developed an interest to study the prevalence of quid induced oral lichenoid reactions in the population of western India. Methods: A total population of 4981 males and females was screened for tobacco use and the prevalence of lesion in 86 quid users was seen. The lesions which met the selection criteria of oral lichenoid reaction were identified. Results: Prevalence of 10.4% oral lichenoid reaction was seen in all quid users and 28.12% in subjects who used tobacco with quid. Statistical analysis yielded a high degree of correlation between occurrence of lesion and quid habit. Conclusions: The clinician should be aware of the occurrence of such lesions and their associated clinical behaviour and malignant potential, if any. A close monitoring/follow-up should be done. [ABSTRACT FROM AUTHOR]

Betel quid is used by 10-20% of world of population. Oral submucus fibrosis (OSF) is a chronic premalignant disease common in South Asian countries where betel quid is chewed. It is characterized by juxtaepithelial fibrosis of oral cavity and limited mouth opening, which can cause difficult intubation. A recent study in Taiwan has revealed long-term betel nut chewing is not predictor of difficult intubation. We describe two cases of OSF and critically analyze this study and its implications for clinical practice. OSF is now seen in Saudi Arabia and western countries with use of commercial betel quid substitutes. Although betel quid without tobacco is used in Taiwan, available evidence suggests rapid and early development of OSF where commercial chewing products like Pan Masala are used in India. Effects of betel quid may vary depending on the composition of quid and chewing habits. Studies where personal habits are involved must be analyzed carefully for external validity. Even though, Taiwan study is controlled, its validity outside Taiwan is highly questionable. Since OSF can cause unanticipated difficult intubation, thus during preanesthetic assessment, history of betel quid chewing, more importantly use of commercial chewing products is more likely to give clues to severity of OSF and possible difficult intubation. Further controlled trails in populations where commercial chewing products are used is necessary to detect association of chewing habits and difficult intubation. [ABSTRACT FROM AUTHOR]

Background: Although tobacco deaths rarely make headlines, tobacco kills one person every six seconds. Tobacco kills a third to half of all people who use it, on average 15 years prematurely. Aim of the Study: To study the risk of oral cancer associated with gutka consumption and other tobacco products. Objective: (1) To find the association between gutka consumption and oral cancer. (2) To study the association between oral cancer and other tobacco products. Methodology: A case-control study of 134 cases and 268 controls, over a period of 5 months, from March 2013 to July 2013, was carried out at the Kasturba medical hospital in Manipal, India. The participants were personally interviewed by the investigator using a structured questionnaire on consumption of tobacco, poly-ingredient dip products, alcohol, dietary practices, oral hygiene practices and demographic status. Results: Univariate logistic regression followed by multivariate logistic regression was done for identifying the risk factors and adjusted for the confounding variables. Analysis showed that gutka (<0.001, OR = 5.195% CI = 2.0-10.3), chewing tobacco (P < 0.001, OR = 6.095% CI = 2.3-15.7), supari (P < 0.001, OR = 11.4 95% CI = 3.4,38.2), betel quid (P < 0.001, OR = 6.4 95% CI = 2.6-15.5), bidi (P < 0.05, OR = 2.3 95% CI = 1.1-4.8) and alcohol (P < 0.001, OR = 3.7 95%CI = 1.8-7.5) had strong association with oral cancer upon adjustment. Conclusion: The study provided strong evidence that gutka, supari, chewing tobacco, betel quid, bidi and alcohol are independent risk factors for oral cancer. [ABSTRACT FROM AUTHOR]

Betel quid is one of the most commonly used psychoactive substances in the world, especially among Asian communities, just after caffeine, nicotine and alcohol. The mixture that is chewed usually contains betel leaves, areca nut and slaked lime, nonetheless, its ingredients and the preparation manner tend to vary. Areca nut contains four main alkaloids - arecoline, arecaidyne, guvacine and guvacoline that are responsible for its psychoactive effects. The act of betel chewing might have a negative impact on an overall health and can cause pathological lesions or diseases to develop and/or progress, both directly and indirectly. Also, it may happen that the negative impact of betel chewing on one system might have indirect harmful influence on another. Still an association has been drawn between betel chewing and the presence of metabolic diseases, cancers and proteinuria, as well as cardiovascular disorders - including hypertension, chronic renal failure, diabetics type II and obesity. Likewise, it is a known risk factor in the development of oral and esophagus cancer. Moreover, a correlation between betel chewing and smoking exists in that betel chewing might theoretically hinder the abandonment of tobacco smoking. Tissues of oral cavity and the upper part of digestive system are additionally exposed to the mechanical injuries caused by the areca nut. Therefore, they tend to be the most prone to be pathologically affected by betel quid chewing. [ABSTRACT FROM AUTHOR]

Background: Betel nut is commonly used in many countries. Despite evidence suggesting an association with asthma, few studies have investigated the connection between betel nut use and asthma; thus, the underlying mechanism for the association with asthma is also unclear. The aim of this study was to investigate the association between betel chewing and asthma as well as the associations of plasma arecoline (a biomarker for exposure) and eotaxin-1 (a potential mediator) with asthma and lung function. Methods: We recruited 600 hospital-based asthmatic patients and 1200 age- and gender-matched community controls in southern Taiwan. To clarify the mechanism of action for eotaxin-1 in the association between betel chewing and asthma, we also designed an in vitro experiment to study the functional associations between arecoline exposure and eotaxin-1 levels. Results: A significant association was found between asthma and current betel chewing (adjusted odds ratio 2.05, 95% CI = 1.12–3.76), which was independent of potential confounders but was attenuated following adjustment for eotaxin-1. Arecoline and eotaxin-1 levels were positively correlated (Spearman r = 0.303, p = 0.02), while arecoline and arecaidine were negatively correlated with lung function. Functionally, arecoline alone does not induce eotaxin-1 release in vitro from dermal and gingival fibroblasts. However, in the presence of IL-4 and TNF-alpha, arecoline at 100 μg/ml induced more eotaxin-1 release than arecoline at 0 μg/ml (2700±98 pg/ml vs 1850±142 pg/ml, p = 0.01 in dermal fibroblast cells, and 1489±78 pg/ml vs 1044±95 pg/ml, p = 0.03 in gingival fibroblast cells, respectively). Conclusion: Betel chewing is associated with asthma in this population, with arecoline induction of eotaxin-1 supported as a plausible causal pathway. [ABSTRACT FROM AUTHOR]

Tobacco smoking, betel quid chewing and alcohol drinking are oral cancer risk factors. Observational studies unanimously report that oral cancer risk in smoking-drinking-chewing exposed subjects is exceptionally high. However, none of them assessed the fractions of this risk attributable to the three individual risk factors and to the smoking-drinking-chewing interaction. The present study sought to assess the magnitude of the smoking-drinking-chewing interaction effect on oral cancer. A meta-analysis of observational South-East Asian studies which reported oral cancer odds ratios (ORs) stratified for smoking-drinking-chewing exposures was performed. The pooled ORs were estimated and controlled for quality, heterogeneity, publication bias and inclusion criteria. The smoking-drinking-chewing interaction effect was estimated through the pooled Relative Excess Risk due to Interaction (RERI, excess risk in smoking-drinking-chewing exposed individuals with respect to the risk expected from the addition of the three individual risks of smoking, drinking and chewing). Fourteen studies were included with low between-study heterogeneity. The pooled ORs for smoking, drinking, chewing, smoking-drinking-chewing, respectively were 3.6 (95% confidence interval −95% CI, 1.9–7.0), 2.2 (95% CI, 1.6–3.0), 7.9 (95% CI, 6.7–9.3), 40.1 (95% CI, 35.1–45.8). The pooled RERI was 28.4 (95% CI, 22.9–33.7). Among smoking-drinking-chewing subjects, the individual effects accounted for 6.7% (smoking), 3.1% (drinking), 17.7% (chewing) of the risk, while the interaction effect accounted for the remaining 72.6%. These data suggest that 44,200 oral cancer cases in South-East Asia annually occur among smoking-drinking-chewing exposed subjects and 40,400 of these are exclusively associated with the interaction effect. Effective oral cancer control policies must consider concurrent tobacco smoking, alcohol drinking, betel quid chewing usages as a unique unhealthy lifestyle. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we provided an empirical examination of the interaction between people's health risk perception and betel chewing. We hypothesized that a better knowledge of possible health risks would reduce both the number of individuals who currently chew betel and the likelihood of those who do not yet chew betel to begin the habit. We constructed a simultaneous equation model with Bayesian two-stage approach to control the endogeneity between betel chewing and risk perception. Using a national survey of 26,684 observations in Taiwan, our study results indicated that better health knowledge reduced the possibility that people would become betel chewers. We also found that, in general, betel chewers have a poorer health risk perception than other population. Overall, the empirical evidence suggested that health authorities could reduce the odds of people becoming betel chewers by improving their knowledge of betel-chewing's harmful effects. [Copyright &y& Elsevier]

Oral submucosus fibrosis (OSMF) is a collagen-related disorder seen in habitual betel quids and smokers. This is a high risk precancerous condition in which the connective tissue fibers of the lamina propria and deeper parts of the mucosa becomes stiff with restricted mouth opening. Patients with severe cases have symptoms like difficulties in chewing, swallowing and speaking. In the present study 25 individuals were gutkha chewers and 25 were OSMF patients (chewing gutkha along with smoking) and 25 individuals were taken as controls. A significant increase in the frequency of micronuclei was observed in OSMF patients (34.4 ±1.79) as compared to gutkha chewers (14.4 ± 0.73) and controls (4.36 ± 0.27). The number of micronucleated cells in OSMF, gutkha chewers and control groups were 19.84 ± 0.69, 12.6 ± 0.51 and 4.20 ±0.27, respectively and are significantly different at p < 0.05. Acridine orange is used due its fluorescence nature and easier visibility of the micronucleus present in the buccal epithelial cells. It is concluded that chewing gutkha along with smoking is more dangerous for human health as it hastens the incidence of OSMF. [ABSTRACT FROM AUTHOR]

Abstract: Oral squamous cell carcinoma (OSCC) is an aggressive cancer and its occurrence is closely related to betel nut chewing in Taiwan. However, there are few prognostic and diagnostic biomarkers for this disease especially for its association with betel nut chewing. Recent progresses in quantitative proteomics have offered opportunities to discover plasma proteins as biomarkers for tracking the progression and for understanding the molecular mechanisms of OSCC. In present study, plasma samples from OSCC patients with at least 5-year history of betel nut chewing and healthy donors were analyzed by fluorescence 2D-DIGE-based proteomic analysis. Totally, 38 proteins have been firmly identified representing 13 unique gene products. These proteins mainly function in inflammatory responses (such as fibrinogen gamma chain) and transport (Apolipoprotein A–I). Additionally, the current quantitative proteomic approach has identified numerous OSCC biomarkers including fibrinogen (alpha/beta/gamma) chain, haptoglobin, leucine-rich alpha-2-glycoprotein and ribosomal protein S6 kinase alpha-3 (RSK2) which have not been reported and may be associated with the progression and development of the disease. In summary, this study reports a comprehensive patient-based proteomic approach for the identification of potential plasma biomarkers in OSCC. The potential of utilizing these markers for screening and treating OSCC warrants further investigations. [Copyright &y& Elsevier]

Abstract: Chewing betel quid may release chemical carcinogens including xenobiotics resulting in oral malignancy cases preceded by potential malignant lesions and conditions — Oral Submucous Fibrosis (OSF) being one of them. The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes the nitrosamines and tannins. The present study investigated the association of polymorphisms at CYP1A1m1 (T3801C), m2 (A2455G), and CYP2E1 PstI site (nucleotide 21259) with the risk of OSF. The study was conducted on 75 OSF patients and 150 controls from an eastern Indian population. The above polymorphisms were analyzed by PCR-RFLP method. Analyses of data show that polymorphisms in CYP1A1m2 [OR=8.25 (4.31–15.80)]; CYP1A1m1 [OR=2.88 (1.57–5.24)] and CYP2E1 PstI site [OR=3.16 (1.10–9.04)] revealed significant association with OSF. Our results suggest that polymorphism in CYP1A1 and CYP2E1 may confer an increased risk for Oral Submucous Fibrosis. [Copyright &y& Elsevier]

Summary: Objectives: Angiotensin I-converting enzyme (ACE), a type I cell surface zinc metallopeptidase, is differentially expressed in several malignancies and plays a role in tumor cell proliferation, tumor cell migration, angiogenesis, and metastatic behavior. We aimed to investigate the effects of ACE gene (rs1799752) variants on oral cancer risk. Materials and Methods: Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) 32 was used to measure ACE gene polymorphisms in 88 patients with oral precancerous lesion (OPL), 186 33 patients with oral cancer, and 120 control subjects without any oral lesions. All study subjects were male 34 betel quid chewers. Results: Patients with oral cancer or OPL had a higher frequency of the DD genotype than the control patients did. Oral cancer patients with the DD genotype had a significantly higher prevalence of lymph node metastases than patients with the II/ID genotype did. After adjusting for age, smoking, drinking, and betel quid chewing status, we found that individuals with the DD genotype of the ACE gene had a 5.46-fold and 3.13-fold higher risk of developing oral cancer or OPL, respectively, than those with the II genotype did. Furthermore, oral cancer patients with the DD genotype of the ACE gene had a 2.16-fold higher likelihood of lymph node metastasis. Conclusion: Our data suggest that the ACE gene polymorphisms may be associated with increased susceptibility to OPL and oral cancer and lymph node metastasis from oral cancer. [ABSTRACT FROM AUTHOR]

Purpose: Non-metastatic stage IV oral cavity cancer patients undergoing concurrent chemoradiotherapy (CCRT) are at risk of malnutrition because of postoperative eating problems and CCRT-related complications. A high percentage of betel quid use, which is associated with metabolic disorders, is found in oral cavity cancer patients in Taiwan. The aim of this study is to evaluate the effect of an early and intensive nutritional support program, comprising individualized counseling, nasogastric tube feeding, and mandatory hospitalization, throughout the CCRT period for such cases in an area where betel quid use is prevalent. Methods: We retrospectively analyzed 35 patients with nutritional support (NI) and 23 patients with no specifically designed nutrition program (NC). Results: The NI group had better maintenance of body weight ( p < 0.001) and higher serum albumin levels ( p < 0.002) than the NC group. There was no difference in the total dose of radiation completed in the two groups; in contrast, the percentage of NI group patients who had radiation therapy (RT) breaks was lower and who completed planned chemotherapy was higher than in the NC group. Furthermore, more NC group patients suffered from sepsis during the treatment period, and fewer were alive 2 years after treatment. Conclusions: An early and intensive nutrition support may be beneficial to minimizing body weight loss, offering better treatment tolerance and probable survival benefits for patients with non-metastatic stage IV oral cavity cancers undergoing CCRT in endemic betel quid chewing areas. [ABSTRACT FROM AUTHOR]

Background Betel quid is chewed by 600 million people worldwide and it has been linked to obesity and cardiovascular disease. The purpose of our study was to examine the prevalence and predictors of betel quid chewing in a rural area of Bangladesh, and determine its effects on body mass index (BMI) and blood pressure.Methods In this population-based prospective study, we analysed data on 19 934 Bangladeshi adults. Linear and multivariate logistic regression was used to determine the socio-demographic predictors of betel quid chewing and the effect of betel quid on change in BMI and on systolic and diastolic blood pressure, pulse pressure, arterial pressure, overweight or obesity, and hypertension.Results At baseline, betel quid was chewed by 33.2% of the cohort (35.5% of men, 31.6% of women). In a subsample in which we collected methods of use, 17.5% chewed it without tobacco and 82.5% chewed it with tobacco. In multivariate analysis, betel quid chewing was associated with female sex, older age, tobacco smoking and lower socio-economic status, as measured by fewer years of formal education and not owning land. Betel quid was chewed more times per day among women and older persons. At follow-up, persons who chewed betel quid without tobacco had higher systolic blood pressure, diastolic blood pressure and arterial pressure in comparison with never users. After controlling for other explanatory variables, chewing betel quid without tobacco was associated with general hypertension [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.04–2.10] and systolic hypertension (OR 1.55, 95% CI 1.01–2.37). We did not observe associations of betel quid chewing with BMI or overweight.Conclusions Betel quid chewing is likely contributing to high blood pressure in Bangladesh, particularly among women. [ABSTRACT FROM AUTHOR]

Abstract: Background: Betel quid is a substance that commonly used among male labor in Taiwan, and the dependence potential has been reported in some studies, but no instrument has been developed specifically to assess areca/betel quid dependence. Objective: To develop a reliable and valid research instrument/screening tool for the measurement of betel quid dependence. Methods: There were 223 male prisoners with a history of betel quid chewing behavior before they were incarcerated in Kaohsiung Prison enrolled in this study. The items of the Betel Quid Dependence Scale (BQDS) were developed by the authors and were designed referring to previous research findings and the diagnostic criteria of Substance Dependence in DSM-IV. Results: The BQDS has high internal consistency (Cronbach''s α =0.921), and a three-factor structure consisting of “physical and psychological urgent need,” “increasing dose” and “maladaptive use,” which accounted for 61.2% of the total variance. There were 94 (42.2%) male-prisoners who satisfied DSM-IV criteria for dependent use, and the receiver operating characteristic (ROC) curve showed that the BQDS had an optimal cut-off score of 4, the optimal sensitivity was 0.926 and the specificity was 0.977, with the predictive accuracy up to 99.3%. Conclusions: The BQDS has good internal consistency and construct validity, and was proved to have optimal reliability and criterion validity in this special sample. Further investigation is suggested in different samples such as the general population or oral submucous fibrosis (OSF) patients to test the generalization of this instrument. [Copyright &y& Elsevier]

Although Madagascar is geographically disjunct from Southeast Asia, Micronesia and Melanesia, where intentional blackening of teeth used to be ubiquitous, this study found the practice deeply rooted in Malagasy culture. Men and women accomplished teeth blackening not only by chewing various, mostly endemic, plants, but also by applying organic burn products as well as a combination of mineral rich soil and barks containing tannins. The highly developed oral literature of Madagascar, in which teeth blackening features frequently, provides material to study the diverse associations which the practice and the requisite plants evoked. These connotations reached from the overtly sexual to affirmations of various core cultural values. For example, when teeth blackener was removed again from frontal teeth to render them white, while keeping molars blackened, this pattern not only held esthetic appeal, but also somatically expressed a desire for concealment versus revelation of the private self. The widespread distribution of teeth blackening across the island and similarities to methods known from Austronesian speakers elsewhere are some of the indications that teeth blackening might have reached Madagascar during its early phases of settlement by Austronesian speakers from the Indo-Malay archipelago. Surprisingly, betel chewing, a practice equally associated with Southeast Asian people, appears to have reached Madagascar at a relatively late date by way of the Swahili coast. Neither areca nut (Areca catechu L.) nor betel pepper (Piper betle L.) become naturalized across the island, nor did the usage of these plants penetrate Malagasy culture to any great extent. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2011) 40: 684-692 Background: Recognition of how risk factors affect the age when cancers are first diagnosed may help to establish more appropriate cancer screening and preventive strategies. Methods: To investigate the independent and synergistic effects of alcohol, tobacco-free betel-quid (TF-BQ), and cigarette use on diagnosis age and dissemination of upper aerodigestive tract squamous cell carcinoma (UADT-SCC), we recruited pathology-proven 1522 patients with UADT-SCC for study. Results: A 49-, 53-, 57-, and 62-year-old stepwise older median age at carcinoma diagnosis was, respectively, found among patients with oral, pharyngeal, esophageal, and laryngeal cancer. Oral cavity (53.2%) and larynx (11.6%) were separately the dominant and recessive sites where the UADT-SCC occurred. Although alcohol and tobacco bestowed increased risks of earlier tumor occurrence only for oral/pharyngeal and oral cancers, respectively, TF-BQ was consistently observed to confer elevated age-associated risks for each UADT-SCC [adjusted hazard ratio (aHR) = 1.6-2.3]. Alcohol and TF-BQ joint consumers experienced a stepwise increased cumulative risk (CR) of contracting carcinomas of the larynx (46.2%), esophagus (47.5%), pharynx (53.5%), and oral cavity (60.5-71.0%), with >68% of CRs found among drinkers who started chewing before age 20. Alcohol + Betel + Cigarette and Alcohol + Betel users exhibi-ted earlier diagnosis ages than non-users: 10 years ahead for oral cancer, 7, 17, and 12 years earlier for pharyngeal, esophageal, and laryngeal cancers. Noticeably, higher cumulative cancer risks regarding earlier tumor occurrence were correspondingly identified for these users aged 43, 49, 43, and 44 upward. Conclusions: Tobacco-free betel-quid, in conjunction with alcohol and/or tobacco consumption, impacts early cancer occurrence for specific UADT-SCC and influences tumor site incidence pattern of these neoplasms. [ABSTRACT FROM AUTHOR]

Oral cancer is the fourth common male cancer and causally associated with environmental carcinogens in Taiwan. The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) has a significant effect on tumorigenesis by limiting angiogenesis and invasion of tumors through the extracellular matrix. RECK downregulation has been confirmed in many human cancers and associated with lymph node metastasis clinically. In the present hospital-based case-controlled study, the demographic, RECK genotype and clinicopathologic data from 341 male oral cancer patients and 415 cancer-free controls were investigated. We found that RECK rs10814325, rs16932912, rs11788747 or rs10972727 polymorphisms were not associated with oral cancer susceptibility. Among 488 smokers, RECK polymorphisms carriers with betel quid chewing have a 7.62-fold [95% confidence interval (CI), 2.96–19.64] to 25.33-fold (95% CI, 9.57–67.02) risk to have oral cancer compared with RECK wild-type carrier without betel quid chewing. Among 352 betel quid chewers, RECK polymorphisms carriers with smoking have a 6.68-fold (95% CI, 1.21–36.93) to 18.57-fold (95% CI, 3.80–90.80) risk to have oral cancer compared with those who carried wild-type without smoking. In 263 betel quid chewing oral cancer patients, RECK rs10814325 polymorphism have a 2.26-fold (95% CI, 1.19–4.29) risk to have neck lymph node metastasis compared with RECK wild-type carrier. These results support that gene–environment interactions between the RECK polymorphisms, smoking and betel quid may alter oral cancer susceptibility and metastasis. [ABSTRACT FROM AUTHOR]

Abstract: Several studies have reported increased skin lesions in betel quid (a mixture of Piper betel leaves, areca nut, tobacco/flavoured tobacco, lime) chewers compared to non-chewers, exposed to arsenic (As) contaminated drinking water in Bangladesh and India. The current study has determined As, cadmium (Cd) and lead (Pb) levels of betel quids and its components using inductively coupled plasma mass spectrometry (ICP-MS). The highest concentrations of As were found in slaked lime (4.56mgkg−1) followed by Piper betel leaves (0.406mgkg−1) and flavoured tobacco (zarda) (0.285mgkg−1), with a mean concentrations of As in betel quids of 0.035mgkg−1 (SD 0.02mgkg−1). Mean concentrations of Cd and Pb in ordinary quids were 0.028 (SD 0.07mgkg−1) and 0.423 (SD 1.4mgkg−1), respectively. We estimated that a daily intake of 6 betel quids could contribute 1.2, 1.9 and 8.5% of the provisional maximum tolerable daily intake (PMDTI) for As, Cd and Pb, respectively. Since betel quid chewing is most prevalent among women, our finding raises concern that women chewers – especially pregnant chewers – may be harming their health and that of their unborn babies through increased exposure to a mixture of toxic elements (As, Cd and Pb). [Copyright &y& Elsevier]

Background: A relationship between betel quid chewing in Bangladeshi populations and the development of skin lesions and tremor has been previously reported, for people exposed to high levels of arsenic (As) through drinking contaminated groundwater. Exposure to manganese (Mn) is also known to induce neurotoxicity and levels of Mn in Bangladeshi groundwater are also high. The present study evaluates betel quid chewing as an overlooked source of Mn exposure in a Bangladeshi population. Methods: Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine (1) urinary Mn levels for 15 chewers and 22 non-chewers from the ethnic Bangladeshi community in the United Kingdom, and (2) Mn levels in betel quids, its individual components and other Bangladeshi foods. Results: Betel quid chewers displayed a significantly higher (P = 0.009) mean Mn concentration in urine (1.93 μg L-1) compared to non-chewers (0.62 μg L-1). High levels of Mn were detected in Piper betel leaves with an overall average of 135 mg kg-1 (range 26 -518 mg kg-1). The mean concentration of Mn in betel quid was 41 mg kg-1 (SD 27) and the daily intake of Mn in the Bangladeshi population was estimated to be 20.3 mg/day. Chewing six betel quids could contribute up to 18% of the maximum recommended daily intake of Mn. Conclusion: We have demonstrated that Mn in betel quids is an overlooked source of exposure to Mn in humans. Chewers display a 3.1 fold increased urinary Mn concentration compared to non-chewers. The practice of betel quid chewing contributes a high proportion of the maximum recommended daily intake of Mn, which could make chewers in Bangladesh more vulnerable to Mn neurotoxicity. [ABSTRACT FROM AUTHOR]