Betel Nut Consumption Research Articles

Substance use and esophageal neuroendocrine neoplasm: A case-control study.

Esophageal neuroendocrine neoplasms (NEN) are extremely rare and little is known about their risk factors. To identify the potential risk factors, we evaluated whether the history of substance use, including alcohol, tobacco and areca nut consumption was associated with esophageal NEN. Forty-one esophageal NEN patients diagnosed between 2002 and 2019 from 17 hospital in Taiwan were enrolled as the cases. Controls were participants who received complete esophagogastroduodenoscopy in an endoscopic cohort and 123 eligible controls were matched to 41 cases (3:1) on age and gender. Alcohol drinking and cigarette smoking significantly increased the risk of esophageal NEN, with about a fourfold risk increase in alcohol drinkers as well as cigarette smokers. Moreover, use of cigarette smoking and alcohol consumption in combination demonstrated the highest risk of esophageal NEN with the risk increasing up to 20 times compared with non-users. Alcohol consumption and cigarette smoking significantly increase risk of esophageal NEN and both alcohol and cigarette users had the highest risk.

Analysis correlation of betel nut consumption behaviour with dental caries in poor communities in Kupang Regency (West Timor)

Introduction: Dental caries is one of the diseases that becomes a burden of disease whose background is caused, among others, by low socioeconomic status. If coupled with lifestyle behaviors that are not beneficial for health such as consuming betel nut, then the burden of life for the poor will get worse. The aim of this research to analysis correlation between betel chewing behaviour and dental caries in low income community. Methode: This type of research is observational-analytic, with a cross-sectional design. To determine the low income community, researchers collaborate with village heads, with the following provisions: low income is a community that receives assistance from the government. The measurement of the caries rate in accordance with the provisions of WHO (2012) is to calculate the DMFT with predetermined criteria regarding the caries rate, Very low, Low, Moderate, High, Very High. By using the formula Lameshow, obtained a sample of 363 and each sub-district around 91 respondents. Result: There is no relationship between the behavior of consuming betel nut with the incidence of dental caries. There is no relationship between occupation and the behavior of consuming betel nut in. There is no relationship between education and betel nut consumption behavior.

A novel approach to develop an animal model for oral submucous fibrosis

Epidemiological data have proved the association of consumption of areca nut with the causation of oral submucous fibrosis (OSF). OSF is a chronic inflammatory disease with the potential for malignant transformation from 7 to 13%. The establishment of animal models makes it easier for researchers to focus on the therapeutic options to combat this disease further. We developed and compared two areca nut extract (ANE) administration methods in Swiss albino mice to establish OSF. This study compared an invasive intrabuccal injection technique with a non-invasive intraoral droplet administration. The duration of induction was around 12weeks. Histopathology (H&E, Masson's trichrome staining) and gene expression analysis (COL-I, COL-II, and α-SMA) were performed using RT-PCR to confirm the OSF in animals. Our study showed that ANE administration through the intraoral droplet method exhibited significantly higher fibrosis than the intrabuccal injections, as evidenced by the H&E and Masson's trichrome staining. Furthermore, intraoral administration of ANE significantly upregulated the mRNA expression of COL-I, COL-II, and α-SMA, as revealed by the RT-PCR analysis. The non-invasive droplet method could simulate the absorption of areca nut seen in humans through daily dosing. This study establishes the intraoral droplet method as an efficient and non-invasive method to administer the ANE to develop OSF. These findings will aid in the efficient development of OSF animal models for interventional studies, including screening novel drugs in the reversal of the OSF.

Potentially -malignant disorders

It is estimated that more than one million new oral cancer cases are being detected annually in the Indian subcontinent, of which 90% are oral squamous cell carcinoma (OSCC). Oral potentially malignant disorder (OPMD) are associated with increased rate of occurrence of OSCC of lips or oral cavity. Transformation of oral cancer from OPMD is common, especially in South Asian countries like India, where tobacco and arecanut consumption is prevalent. Early diagnosis and timely treatment of PMD’s may help to prevent its malignant transformation into oral cancer. The aim of the article is to highlight the risk factors, etiology, clinical presentation of PMD, thus helps in early detection and treatment, thereby reducing incidence of oral cancer.

KEPUTUSAN DAN PREFERENSI KONSUMEN : PINANG KERING IRIS DI PERBATASAN (StudiKasus: Kabupaten Timor Tengah Utara)

Betel nut consumption in North Central Timor Regency lasted a long time and continues to grow to this day. The study aims to determine the factors that influence consumer decisions and consumption preferences of iris dried betel nut in north Central Timor border communities. This research was conducted in January-February 2022.The data analysis method used is qualitative descriptive and logistic regression analysis. The variables of age, sex, habits, taste, and texture together affect the consumption preferences of iris dried betel nut. The age and texture of the iris dried betel nut significantly affect the decision of the people of East Miomaffo Subdistrict in consuming slice dry betel nut. Texture becomes the preference of consumers to choose the dried betel nut of the iris consumed.

Biochemical profile alterations of lipids in oral submucous fibrosis

Oral Submucous Fibrosis (OSMF) in India has been attributed to the increased consumption of areca nut. Oral Submucous Fibrosis (OSMF) is a chronic disease of the oral cavity which is characterized by an epithelial and sub epithelial inflammatory reaction followed by fibro elastic changes in the mucosa. The present study was aimed to estimate serum lipid profile i.e. Total cholesterol (TC), Triglycerides (TG), High Density Lipoprotein (HDL-C), Low Density Lipoprotein (LDL-C), Very Low Density Lipoprotein (VLDL-C) in Moderate Oral Submucous Fibrosis and compared with controls. The study subjects were divided into 2 groups i.e. Group-I (Moderate Oral Submucous Fibrosis), Group-II (controls). Group-I includes n=50 patients of clinically diagnosed and histopathologically proven of Moderate Oral Submucous Fibrosis. They were in the age group of 20-45 years. Group-II (controls) were age and sex-matched, apparently healthy volunteers (n=50) were included in this study. Serum lipid profile was analyzed in all study subjects using by Randox Rx daytona Auto Analyzer. The present study showed statistically significant decreased serum levels of Total Cholesterol (TC), Triglycerides (TG), High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C) and Very Low Density Lipoprotein Cholesterol (VLDL-C) levels in group-I when compared with group-II. The changes in lipid profile have long been associated with cancer because lipids play key role in maintenance of cell integrity.

Upregulation of anaphase promoting complex (APC) 7 as a prognostic marker for esophageal squamous cell carcinoma: A hospital based study

Esophageal cancer is the sixth leading cause of cancer death, and esophageal squamous cell carcinoma (ESCC) is the most prevalent type worldwide, with a poor prognosis due to late diagnosis. The search for new molecular prognostic biomarkers revealed that dysregulation of anaphase promoting complex/cyclosome (APC/C) activation due to altered expression of APC molecules might lead to perturbed mitotic progression leading to malignancy. We analyzed the expression of the four different subunits of the APC/C complex—APC3, APC4, APC5 and APC7—by Real Time Polymerase Chain Reaction (RT–PCR). The findings were then correlated with clinicopathological parameters and different lifestyle factors. Significant upregulation of APC7 (tissue and blood: N = 50; 3.72 ± 1.21 and 4.45 ± 1.18, respectively) and APC3 (tissue and blood: N = 52 and 55 and 4.50 ± 1.41 and 4.58 ± 1.06, respectively) suggests their role in uncontrolled cell proliferation. In addition to their association with increasing age, their significant association with tumor size, node stage (only APC7 (p < 0.05)), and dysphagia grade supports a potential role in tumorigenic transformation in ESCC. Furthermore, several exclusive lifestyle-associated factors play a crucial supporting role in the development of ESCC in the Northeast Indian population. Various lifestyle factors, such as the duration of smoking, tobacco and betel nut consumption, and the duration of alcohol consumption, are significantly associated with the expression of APC. Analysis based on Pearson's correlation coefficient indicated a positive correlation among the gene expression levels ofAPC3 (both blood and tissue), APC5 (tissue) and APC3 (tissue), APC7 (tissue) and APC3 (tissue), and APC7 (tissue) and APC3 (blood). Additionally, a positive correlation was found between APC7 expression in blood and tissue samples. However, no significant correlation was found between APC 7 expression and APC4 and APC5 expression in either blood or tissue samples.

Pyknotic Cell Features of Buccal Mucosal Smear in Various Oral Lesions of Betel Nut Chewers

The habit of chewing betel nut is one of the predisposing factors that can trigger the formation of various oral lesions and develop into a malignant condition in the form of oral squamous cell carcinoma (OSCC). This malignancy has a low five-year survival rate as early detection is not widely carried out. Early detection can be conducted by examining pyknotic cells to describe the level of apoptosis. This study aims to examine the pyknotic cell features as a marker of apoptosis in various oral lesions found in betel nut chewers. This study is an analytic survey conducted once with a post-test control group design. The study was conducted on 17 betel nut chewers and 17 healthy people as controls. A buccal mucous smear was collected, and cytological slides were made with Papanicolaou stain. Pyknotic cells were counted using a light microscope and Optilab pro camera. This study found several oral lesions in betel nut chewers, namely exogenous pigmentation, lesions resembling leukoplakia, and lichenoid reaction. Furthermore, the result also showed that the frequency of pyknotic cells in betel nut chewers was lower than in the control group. Non-parametric Kruskal Wallis and post hoc Mann Whitney test showed significant differences in the number of pyknotic cells in various oral lesions with a p-value = 0,001. It can be concluded that the consumption of betel nut affected the level of apoptosis, characterized by a decrease in pyknotic cells and significantly different pyknotic cells depending on the type of oral lesions.

Expression of Sex Hormones in Oral Squamous Cell Carcinoma: A Systematic Review on Immunohistochemical Studies.

Oral squamous cell carcinoma (OSCC) is the most widespread oral malignancy. In the western world, smoking and alcohol remain the most common risk factors, whereas smokeless tobacco and areca nut consumption are the prevalent etiological factors in South Asia. Numerous markers were studied till date to identify the disease. However, the role of sex hormones in OSCC is poorly defined. Hormonal receptors play a role in breast cancer, prostate cancer, and human papillomavirus (HPV) driven oropharyngeal cancers. It is proven that the expression of estrogen receptor-α improved the overall survival of the patient with HPV-positive oropharyngeal cancer. Thus, this review article aims to determine the expression of sex hormones by immunohistochemistry in OSCC.This systematic review was performed with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement Criteria 2020. Relevant articles were collected from the electronic database in PubMed and Cochrane till 2021. Immunohistochemical studies on sex hormones and their role in OSCC published in English literature were included. We excluded case reports, case series, and abstract-only articles. The sample size of the selected studies varied, and these studies measured the parameters such as sex hormones and OSCC. Furthermore, all the studies used different sex hormones and their association with oral cancer through the immunohistochemical process. Thus, this review summarizes that sex hormones influence the biopathology of oral cancer and have a prognostic significance in the tumor subgroups.

Evidence of areca nut consumption in the United States mainland: a cross-sectional study

BackgroundAreca nut (AN) is an addictive substance consumed in the Southeast region and is highly associated with oral premalignant lesions and oral cancer. The impact of AN use in the United States (US) is largely unknown, but the products are readily available and probably used by a significant fraction of Asian immigrants or descendants living in the US. We aimed at assessing AN use prevalence among the Asian community in Houston, Texas.MethodsA cross-sectional questionnaire was used to interview adult individuals (≥ 18 years of age) who self-identified as Asian immigrants or descendants residing in Houston. Means, frequencies, and proportions were reported. Factors associated with AN use were evaluated using logistic regression.ResultsWe surveyed 275 individuals (58% women, 43% between 35–54 years old, 67% born outside of the US, and 6% concurrent smokers). Among respondents, 91% were familiar with AN products, 17% self-reported ever use of AN products in the US, and 31% had friends/family members who were AN ever users. AN use was significantly associated with being Indian Subcontinent immigrants or descendants (ISID) (OR = 3·9; CI: 1·10,13·81; p = 0·035) and having friends/family members using AN products (OR = 6·2; CI: 1·69, 22·69; p = 0·006).ConclusionsOur findings provide quantitative data on the prevalence of AN ever use and context for future AN prevention and cessation interventions specific to the Southeast Asian groups living in the US mainland. This is crucial for the prevention and control of oral cancer and other detrimental conditions related to AN consumption.

Keputusan Konsumen Mengkonsumsi Pinang Kering Iris di Kecamatan Kota Kefamenanu Kabupaten Timor Tengah Utara

Consumption of areca nut has become a culture of society in the District of Kota Kefamenanu. Sliced dried areca nut is an option for consumption because it can last a long time. Slice dried arecal nut in Kota Kefamenanu sub-district is divided into two types, namely dry iris batu nut and iris dry muda nut. This study aims to analyze the consumer's decision to consume sliced dried areca batu and slice dry areca muda nut in Kota Kefamenanu District. This research was conducted from September to October 2021. The number of samples used in this study was 150. Consumer decisions in Kefamenanu City were analyzed by logistic regression using software Eviews9. The results showed that psychological factors and texture variables had a significant effect on consumer decisions to consume sliced dried areca nut in Kefamenanu City District.

Health-Related Quality of Life, Psychosocial Distress and Unmet Needs in Older Patients With Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is the most common cancer involving the mucosal surfaces of the head and neck and is associated with a number of etiological factors, including cigarette smoking, alcohol and betel nut consumption and exposure to high-risk human papillomavirus. The risk of HNSCC increases with age, peaking in the seventh and eighth decade, but this varies by anatomical and histological subtype. While several advancements have been made in the treatment of head and neck cancer (HNC) in recent decades, undertaking curative treatment still subjects the majority of HNSCC patients to substantial treatment-related toxicity requiring patients to tolerate a gamut of physical, psychological, and emotional demands on their reserves. In conjunction with other patient-related factors, clinicians involved in treating patients with HNSCC may incorporate advancing chronological age into their decision-making process when determining treatment recommendations. While advancing chronological age may be associated with increased concerns regarding physical treatment tolerability, clinicians may also be concerned about heightened vulnerability in various health and wellbeing outcomes. The available literature, however, does not provide evidence of this vulnerability in patients with advancing age, and, in many instances, older patients self-report greater resilience compared to their younger counterparts. While this data is reassuring it is limited by selection bias and heterogeneity in trial and study design and the absence of a consistent definition of the elderly patient with HNSCC. This narrative review article also includes a review of the measures used to assess HRQL, psychosocial outcomes and unmet needs in elderly or older patients with HNSCC.

Oral Submucous Fibrosis: Association of Clinical and Histological Severity with Hearing Loss and Middle Ear Function.

OSMF is a precancerous condition of the oral cavity. Cons umption of Areca nut in quid has been proved to be the most consistent factor. To assess middle ear function in OSMF patients by audiometry and tympanometry. Two Hundred patients of < 40years of age with OSMF were examined and followed by PTA and impedance audiometry. Impaired mobility was seen in 20(10%) ears, and retraction of tympanic membrane was found in 36(18%) ears. Clinical staging was done in four stages. Majority of the patients were males (58%) in the age group of 21-30years belonging to stage III (38%) and IV (26%) respectively. PTA showed varying degrees of hearing loss in 73 (36.5%) ears. In Grade I, mild hearing loss was seen in 10 (35.71%) ears and moderately severe hearing loss was in 5 (11.36%) ears whereas in Grade II mild hearing loss in 11(25%) ears. Grade III and IV showed mild hearing loss in 11(14.47%) and 12 (23.07%) respectively. Tympanometry revealed type A curve in 126 (63%) ears followed by C curve in 50 (25%) and B curve in 24 (12%) ears. In patients of OSMF, there is involvement of palatal/paratubal muscles in the fibrosis process, which causes eustachian tube malfunction leading to disturbed middle ear functions and negative middle ear pressure. Most patients of oral submucous fibrosis showed direct association with grade of hearing impairment and eustachian tube dysfunction. Higher clinical grades, both clinically and histologically showed similar findings thereby we concluded that if the disease is treated early, preventing patients from having higher grades of disease, involvement of ear can be avoided, and patients can be saved from hearing impairment.

Securin overexpression correlates with the activated Rb/E2F1 pathway and histone H3 epigenetic modifications in raw areca nut-induced carcinogenesis in mice

BackgroundRaw areca nut (RAN) consumption induces oral, esophageal and gastric cancers, which are significantly associated with the overexpression of pituitary tumor transforming gene 1/securin and chromosomal instability (CIN). An association of Securin/PTTG1 upregulation and gastric cancer in human was also demonstrated earlier. Since the molecular mechanism underlying securin upregulation remains unclear, this study intended to investigate the association of securin upregulation with the Rb-E2F1 circuit and epigenetic histone (H3) modification patterns both globally and in the promoter region of the securin gene.MethodsSix groups of mice were used, and in the treated group, each mouse consumed 1 mg of RAN extract with lime per day ad libitum in the drinking water for 60 days, after which the dose was increased by 1 mg every 60 days. Histopathological evaluation of stomach tissues was performed and securin expression was analysed by immunoblotting as well as by immunohistochemistry. ChIP-qPCR assays were performed to evaluate the recruitment of different histone modifications in the core promoter region of securin gene as well as its upstream and downstream regions.ResultsAll mice developed gastric cancer with securin overexpression after 300 days of feeding. Immunohistochemistry data revealed hyperphosphorylation of Rb and upregulation of E2F1 in the RAN-treated samples. Increased trimethylation of H3 lysine 4 and acetylation of H3 lysine 9 and 18 both globally and in the promoter region of the securin gene were observed by increasing the levels of lysine-N-methyltransferase 2A, lysine-acetyltransferase, EP-300 and PCAF after RAN treatment. ChIP-qPCR data revealed that the quantity of DNA fragments retrieved from the immunoprecipitated samples was maximum in the -83 to -192 region than further upstream and the downstream of the promoter for H3K4Me3, H3K9ac, H3K18ac and H3K9me3.ConclusionsRAN-mediated pRb-inactivation induced securin upregulation, a putative E2F1 target, by inducing misregulation in chromatin remodeling in its promoter region, which led to transcriptional activation and subsequent development of chromosomal instability. Therefore, present results have led to the hypothesis that RAN-induced changes in the epigenetic landscape, securin overexpression and subsequent elevation of chromosomal instability is probably byproducts of inactivation of the pRb pathway.

Conventional fibrotomy and reconstruction with lateral thigh dermal fat pad in grade III oral submucous fibrosis patients: A case report and review of literature

Oral submucous fibrosis is a chronic debilitating premalignant condition with progressive stiffening of oral mucosa ultimately ending in trismus most commonly from substance abuse. The most common etiological factor is the consumption of areca nut. Patients usually report to us when the mouth opening is almost nil. Various grafts have been used in the reconstruction of buccal defects after fiberotomy, the most popular being the buccal fat pad. We present the case of a 34-year-old man presenting with the complaint of reduced mouth opening and burning sensation in the mouth for 8 months. The patient is a poor candidate for buccal fat grafting as the patient body type being ectomorphic. The patient had a stigma of scar in the abdomen; hence, the possibility of an abdominal fat graft was out of the equation. Therefore, dermal fat is was harvested from the lateral thigh and reconstructed into the defect. The patient had a favorable outcome with good healing. Further studies are required to assess the quality, microscopic features of the adipose tissue, and the fate of dermal fat from the anterolateral thigh region.

Role of Aloe vera in the management of oral submucous fibrosis

Oral submucous fibrosis (OSMF) is a potentially malignant disorder of the oral cavity commonly prevalent in India and other southeastern countries where consumption of areca nut is predominated. As it has significant morbidity and mortality, early diagnosis and prompt treatment are essential. At present, none of the treatment modalities offers a complete cure for the diseases. Thus, in the search of newer treatment modalities, various Ayurvedic medicines have been studied in recent years. The present review aims to summarize the role of Aloe vera for the treatment of OSMF.

Effect of personal habits on bone mineral density among adults using orthopantomogram indices as a screening tool for osteoporosis

Background: Effect of tobacco, areca nut, and alcohol consumption (vices) on orthopantomogram (OPG) indices. Aims: To assess the relationship between vices on OPG indices in Indian adult males aged 20–60 years. Subjects and Methods: This study was conducted on 172 males with a mean age of 34.2 ± 1 years. OPG was used for measuring mandibular indices and correlated with the history of the presence of vices. Statistical Analysis Used: Data were presented as mean ± SE or frequency (%). Point biserial correlation was used to assess the correlation between OPG indices and vices. Analysis of covariance was used to analyze the differences in age-adjusted OPG indices between males who had vices against males who had no vice. Results: Overall, 21.5% of the males had at least one vice. A significant decrease in antegonial index (AI) values (P < 0.05) was found between tobacco and alcohol consumption. There was a significant decrease in the values of the gonial index (GI) and AI, having at least one vice (P < 0.05). A higher percentage of participants who had at least one adverse habit had low OPG indices score than participants who had no such habits. Conclusions: Orthopantomogram indices specifically AI were negatively affected in males who had vices.

A Clinical Comparative Study with Evaluation of Gustatory Function Among Oral Submucous Fibrosis Patients, Gutka Chewers, Chronic Smokers and Healthy Individuals

Context: Oral submucous fibrosis (OSMF) is a chronic debilitating disease with significant malignant potential. The most common symptoms of the condition include burning sensation, trismus, swallowing, and speech impairment as well as gustatory alteration. Aims: The aim of the study was to evaluate and compare the efficacy of gustatory functions in oral submucous fibrosis patients, gutka chewers, chronic smokers and healthy individuals. Methods and Material: A total of 112 individuals were selected for the study and divided into four groups of 28 participants, each comprising OSMF patients, gutka chewers, chronic smokers with gutka-chewing habits, and healthy individuals. Each participant was assessed for gustatory function using four different tastants for sweet, sour, salty, and bitter, and the taste perception was recorded as hypogeusia, hypergeusia, dysgeusia, and ageusia. Statistical Analysis Used: Data obtained were analyzed with SPSS software version 26. A comparison between the four groups was made separately for the four different tastes and the five parameters. A P value of ≤0.05 was considered statistically significant. Results: For OSMF patients, gutka chewers, and chronic smokers with gutka-chewing habits, salty taste showed normal perception, sweet taste showed hypogeusia, and bitter taste reported ageusia. The healthy individuals mostly showed normal perception for almost all tastes. Conclusions: It can be concluded that OSMF and habitual consumption of areca nut and tobacco appear to have a significant impact on the alteration of the gustatory function, although the type of taste sensation that is affected may vary from person to person.

Label-free quantitation of the changes in salivary proteome associated with the chronic consumption of the betel nut (Areca catechu).

Areca nut or betel nut chewing is most frequently used in Pakistan and is associated with a high risk for oral cancer. Until now, however, there has not been any research conducted on the long-term effect(s) of betel nut chewing on the saliva proteome. In the present study, initially, the changes in the saliva proteome associated with betel nut chewing were investigated. Secondly, the analysis was focused on the changes in salivary proteome with respect to prolonged usage of betel nuts. After extraction, the saliva proteins were digested into peptides and these were subsequently analyzed using mass spectrometry. Data are available via ProteomeXchange with identifier PXD029768. Label-free quantitation of saliva samples revealed a total of 12 proteins that were differentially expressed between betel nut addicts (BNAs), and the control group. The study groups were further divided into three subgroups, the BNA-1, BNA-2, and BNA-3 groups, with respect to the extent of consumption of betel nuts in terms of years. The data analysis revealed a more detailed profiling of proteins expressed after five, ten, and more than ten years of betel nut consumption. A total of 30, 17, and 22 proteins were found to be differentially expressed when divided into the BNA-1, BNA-2, and BNA-3 groups. The present study shows that the chronic usage of betel nuts leads to the expression of proteins, such as SPARC1, profilin, and SBSN, which are known to be involved in head and neck cancers.

An Account of Areca Nut Uses and Oral Health Damages from An Indian Perspective

There is a perception in India that packaged paan masala and betel quid (BQ) with areca nut loosely called paan supari both being devoid of tobacco are not carcinogenic. This article intends to be an awareness initiative against this notion. It focuses on the use of areca nuts in various forms. An understanding is necessary for the identification of components of gutka, various forms of BQ, and paan masala wherein areca nut is used. Areca nut consumption damages oral health and leads to the development of oral submucous fibrosis (OSF). OSF is used as an umbrella term for depicting all potentially malignant lesions. Gutka is a product popular in India that uses areca nuts and a form of flavoured tobacco (zarda) as the main component. Although oral tobacco is implicated as a grade I carcinogen, areca nuts and BQ-containing areca nuts belong to the same grade. Areca nuts are the fourth largest addictive substance in the world. Deleterious effects of areca nuts in various forms are a grossly underreported area of research. Initiatives against areca nut uses are required.