Application of Artificial Intelligence in Measuring Novel pH-Impedance Metrics for Optimal Diagnosis of GERD.

Novel metrics extracted from pH-impedance monitoring can augment the diagnosis of gastroesophageal reflux disease (GERD). Artificial intelligence (AI) is being widely used to improve the diagnostic capabilities of various diseases. In this review, we update the current literature regarding applications of artificial intelligence in measuring novel pH-impedance metrics. AI demonstrates high performance in the measurement of impedance metrics, including numbers of reflux episodes and post-reflux swallow-induced peristaltic wave index and, furthermore, extracts baseline impedance from the entire pH-impedance study. AI is expected to play a reliable role in facilitating measuring novel impedance metrics in patients with GERD in the near future.

Artificial intelligence facilitates measuring reflux episodes and postreflux swallow-induced peristaltic wave index from impedance-pH studies in patients with reflux disease.

BACKGROUND/AIM: Reflux episodes and postreflux swallow-induced peristaltic wave (PSPW) index are useful impedance parameters that can augment the diagnosis of gastroesophageal reflux disease (GERD). However, manual analysis of pH-impedance tracings is time consuming, resulting in limited use of these novel impedance metrics. This study aims to evaluate whether a supervised learning artificial intelligence (AI) model is useful to identify reflux episodes and PSPW index. METHODS: Consecutive patients underwent 24-h impedance-pH monitoring were enrolled for analysis. Multiple AI and machine learning with a deep residual net model for image recognition were explored based on manual interpretation of reflux episodes and PSPW according to criteria from the Wingate Consensus. Intraclass correlation coefficients (ICCs) were used to measure the strength of inter-rater agreement of data between manual and AI interpretations. RESULTS: We analyzed 106 eligible patients with 7939 impedance events, of whom 38 patients with pathological acid exposure time (AET) and 68 patients with physiological AET. On the manual interpretation, patients with pathological AET had more reflux episodes and lower PSPW index than those with physiological AET. Overall accuracy of AI identification for reflux episodes and PSPW achieved 87% and 82%, respectively. Inter-rater agreements between AI and manual interpretations achieved excellent for individual numbers of reflux episodes and PSPW index (ICC = 0.965 and ICC = 0.921). CONCLUSIONS: AI has the potential to accurately and efficiently measure impedance metrics including reflux episodes and PSPW index. AI can be a reliable adjunct for measuring novel impedance metrics for GERD in the near future.

Effect of deep brain stimulation on brain network and white matter integrity in Parkinson's disease.

AIMS: The effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa-treated Parkinson's disease (PD) patients before and after DBS. METHODS: Clinical assessment, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were performed pre- and post-DBS in 15 PD patients, using a within-subject design. The rs-fMRI identified brain network topological metric and FC changes using graph-theory- and seed-based methods. White matter integrity was determined by DTI and tract-based spatial statistics. RESULTS: Unified Parkinson's Disease Rating Scale III (UPDRS- III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre-DBS patients without medication. Post-DBS PD patients showed a significant decrease in the graph-theory-based degree and cost in the middle temporal gyrus and temporo-occipital part-Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI-II) and the FC changes with UPDRS-III scores. CONCLUSION: STN-DBS modulated graph-theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi-modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN-DBS are caused by brain network alterations.

Variation in tube voltage for pediatric neck 64VCT: Effect on radiation dose and image quality.

Exposure to ionizing radiation can cause cancer, especially in children. In computed tomography (CT), a trade-off exists between the radiation dose and image quality. Few studies have investigated the effect of dose reduction on image quality in pediatric neck CT. We aimed to assess the effect of peak kilovoltage on the radiation dose and image quality in pediatric neck multidetector-row CT. Measurements were made using three phantoms representative of children aged 1, 5, and 10 years, with tube voltages of 80, 100, and 120 kilovoltage peak (kVp); tube current of 10, 40, 80, 120, 150, 200, and 250 mA; and exposure time = 0.5 s (pitch, 0.984:1). Radiation dose estimates were derived from the dose-length product with a 64-multidetector-row CT scanner. Images obtained from the control protocol (120 kVp) were compared with the 80- and 100-kVp protocols. The effective dose (ED) was determined for each protocol and compared with the 120-kVp protocol. Quantitative analysis entailed noise measurements by recording the standard deviation of attenuation for a circular 1-cm2 region of interest placed on homogeneous soft tissue structures in the phantom. The mean noise of the various kVp protocols was compared using the unpaired Student t-test. Reduction of ED was 37.58% and 68.58% for neck CT with 100 kVp and 80 kVp, respectively. The image noise level increased with the decrease in peak kilovoltage. Noise values were higher at 80 kVp at all neck levels, but did not increase at 100 kVp, compared to 120 kVp in the three phantoms. The measured noise difference was the greatest at 80 kVp (absolute increases<2.5 HU). The subjective image quality did not differ among the protocols. Thus, reducing voltage from 120 to 80 kVp for neck CT may achieve ED reduction of 68.58%, without compromising image quality.

DIAGNOSTIC REFERENCE LEVELS OF CARDIAC COMPUTED TOMOGRAPHY ANGIOGRAPHY IN A SINGLE MEDICAL CENTER IN TAIWAN: A 3-Y ANALYSIS.

This study aimed to establish the diagnostic reference levels (DRLs) for coronary computed tomography angiography (CCTA) and coronary arterial calcium score (CACS) owing to a large variability in patient radiation dose and the lack of dose recommendations in Taiwan. Volume computed tomography dose index (CTDIvol) and dose-length product (DLP) were obtained using CCTAs and the CACS of 445 patients over a 3-y period in a single medical center in Taiwan. CCTAs were performed using routine protocols and 256-detector CT scanners. Electrocardiogram gating was retrospective. The obtained data were analyzed using Prism 6 to determine the 25th, 50th (median) and 75th DRL percentiles for CTDIvol and DLP. These DRL results were compared with existing DRLs from seven countries. The DRLs for CCTA determined from this survey were similar to the existing data from other countries. Such DRLs could provide a useful tool for the optimization of radiation dose for CCTA in Taiwan.

Extracranial/Intracranial Vascular Bypass in the Treatment of Head and Neck Cancer - Related Carotid Blowout Syndrome.

OBJECTIVE/HYPOTHESIS: To investigate the endovascular intervention or extracranial/intracranial (EC/IC) vascular bypass in the management of patients with head and neck cancer-related carotid blowout syndrome (CBS). STUDY DESIGN: Retrospective case series. METHODS: Retrospective analysis of clinical data of patients with head and neck cancer-related CBS treated by endovascular intervention and/or EC/IC vascular bypass, analysis of its bleeding control, neurological complications, and survival results. RESULTS: Thrity-seven patients were included. Twenty-five were associated with external carotid artery (ECA); twelve were associated with internal or common carotid artery (ICA/CCA). All patients with ECA hemorrhage were treated with endovascular embolization. Of the 12 patients with ICA/CCA hemorrhage, 9 underwent EC/IC bypass, 1 underwent endovascular embolization, and 3 underwent endovascular stenting. For patients with ECA-related CBS, the median survival was 6 months, and the 90-day, 1-year, and 2-year survival rates were 67.1%, 44.7%, and 33.6%, respectively; the estimated rebleeding risk at 1-month, 6-month, and 2-year was 7.1%, 20.0%, and 31.6%, respectively. For patients with ICA/CCA-related CBS, the median survival was 22.5 months, and the 90-day, 1-year, and 2-year survival rates were 92.3%, 71.8%, and 41.0%, respectively; the estimated rebleeding risk at 1 month, 6 months, and 2 years is 7.7%,15.4%, and 15.4%, respectively. ICA/CCA-related CBS patients have significantly longer survival time and lower risk of rebleeding, which may be related to the more use of EC/IC vascular bypass as a definite treatment. CONCLUSIONS: For patients with ICA/CCA-related CBS, if there is more stable hemodynamics, longer expected survival, EC/IC vascular bypass is preferred. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:1548-1556, 2021.

Undersized stent graft for treatment of cephalic arch stenosis in arteriovenous hemodialysis access.

Cephalic arch stenosis (CAS) is a common cause of AV dialysis access failure and is notoriously difficult to treat with conventional venoplasty. Although stent graft (SG) placement has improved patency rate, they are prone to stent failure caused by edge stenosis. We investigate the effect of SG diameter relative to cephalic vein on patency rate among hemodialysis patients with dysfunctional arteriovenous access caused by CAS. We identified 22 patients with recalcitrant cephalic arch stenosis or post-venoplasty vessel rupture and received SG placement. Patients were divided into two groups based on the stent-to-vessel diameter (S/V) ratio: undersized group, < 1; and apposed group, 1-1.2. Outcomes were assessed through follow-up angiography. S/V ratio was significant smaller in the undersized patient group (p < 0.001). Placement of undersized SG demonstrated higher primary stent (p = 0.001) and access patency rates (p = 0.021) and a reduced number of post-treatment reinterventions per access year (p = 0.021). A decreased number of lateral edge stenosis was noted in undersized SG (p = 0.005). Increased S/V ratio was significantly associated with lateral edge stenosis (OR = 5.19; p = 0.027). Undersized SG is associated with higher primary stent and access patency rate, and decreased number of post-SG interventions, and are suggested in the treatment of cephalic arch stenosis.

Graph theory and network topological metrics may be the potential biomarker in Parkinson's disease.

This study used Voxel-based morphometry (VBM) and resting-state functional magnetic resonance imaging (rs-fMRI) to investigate changes in brain structure and networks functional connectivity, respectively. We tried to identify the potential biomarkers in Parkinson's disease (PD) progression. We recruited nine idiopathic PD patients and seven healthy control participants (HC group) who were age-matched to undergo T1-weighted images and rs-fMRI on 1.5 T. Brain structure differences were analyzed by VBM. Topological properties of networks functional connectivity were analyzed by graph theory. Thirty-two nodes of 8 networks and 133 nodes of interest then were identified with graph theory approaches. VBM examinations showed significant decreases of brain gray matter regions including the left temporal lobe, left middle temporal, middle temporal gyrus, parietal lobe, postcentral gyrus, left inferior parietal gyrus, medial frontal gyrus and supplement motor area in PD patients compared to the HC group. The 32 ROI of networks topological metrics measurement in PD demonstrated increases of global efficiency, cost, and degree in frontoparietal PPC (R) network, but decreases of local efficiency, clustering coefficient, and average path length in salience ACC, dorsal attention FEF (L), and salience aInsula (R) networks, respectively. All 165 ROI connectomes showed eight connections intensity changes, that decrease in OP r to frontoparietal PPC, putamen r to cereb11, and SFG l to Ver8 in PD. These results suggest that the graph theory and the network topological metrics measurement may be the potential biomarkers in PD to evaluate the disease progress and to monitor the therapeutic results.

Automatic current selection with iterative reconstruction reduces effective dose to less than 1 mSv in low-dose chest computed tomography in persons with normal BMI.

Most of the recent studies have used fixed tube current while few investigators use automatic current selection (ACS) with iterative reconstruction (IR) techniques to reduce effective dose (ED) to < 1 mSv in low-dose chest computed tomography (LDCCT). We investigated whether image quality of lungs as produced by a fixed tube current (FTC) of 35 mAs can be maintained with ED < 1 mSv produced by ACS with IR techniques in LDCCT. A total of 32 participants were included. The LDCCT was performed by a FTC 35 mAs (with a kilovoltage peak of 120 kVp) in 16 participants (Group A), and by a DoseRight ACS in 16 participants (Group B). Their images were improved by IR technique. The ED was estimated by multiplying the individual dose length product (DLP) by the dose conversion factor. The image quality was assessed by the CT number, noise levels, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the regions of interest in the apex, upper lobe, and lower lobe of lung regions in the CT images. A t-test was used to evaluate the LDCCT image quality between the groups. The ED was significantly 49.2% lower in Group B than in Group A (0.71 ±â€Š0.05 mSv vs 1.40 ±â€Š0.02 mSv, P < .001). However, noise level, SNR, and CNR were not significantly different between Groups A and B, indicating the image quality was similar between two groups, or our setting parameters for DoseRight ACS with IR technique can achieve the image quality as good as obtained on the FTC 35 mAs with IR techniques. Our results suggest that the DoseRight ACS with IR technique reduces ED to lower than 1 mSv (averagely 0.71 mSv) yet maintains an image quality as good as produced by FTC 35 mAs with IR technique in normal BMI persons. The ACS setup thus is more preferable than the FTC to achieve the ALARA (as low as reasonably achievable) principle.

[Using an Information System to Optimize the ACLS Process at the Emergency Department].

The best first-aid treatment for cardiac arrest patients is advanced cardiac life support (ACLS) in terms both of saving lives and of reducing the incidence of sequelae. The American Heart Association (AHA) published updated ACLS guidelines for care in 2015. These updated guidelines emphasized the importance of teamwork in resuscitation, noting that, in addition to standard procedures, team members should be familiar with their distinct roles and should cooperate together during emergent situations. Implementing ACLS is not easy due to stress and unfamiliarity with the process and thus often achieves less-than-optimal results in practice. However, ACLS is a standard approach that uses the same procedures to address different cardiac arrest situations. Therefore, we wanted to use an information system to assist the medical team to fully implement the ACLS process. The information system helps the medical team perform resuscitation actions more intensively and precisely while avoiding problems and mistakes due to forgetfulness / unfamiliarity, facilitating an optimal resuscitation effort. Concurrently, electronic medical and nursing records are completed automatically, avoiding the need for medical staff to compile these records afterwards. This information system helps save time and effort and improves precision. Furthermore, data analysis is more convenient, which facilitates the effective management and supervision of resuscitation quality. The information system performs timing, prompting, and guidance in accordance with the ACLS process and records the procedures that will used in emergency treatment (i.e., chest compression frequency, establishment of intravenous route, placement of endotracheal tubes, electric shock, drug type, dose) with a simple click of a mouse. Finally, the associated medical record is completed and logged as soon as the automatically generated file is uploaded. All hospital staffs may use this information system to assist in the implementation of advanced CPR. The system improves the quality of the first aid measures applied in life support, reduces the burden on clinics and medical staff, and streamlines the preparation and submission of medical records.

Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

Clinical significance of integrin-linked kinase in laryngeal squamous cell carcinoma.

OBJECTIVE: To investigate the expression of integrin-linked kinase (ILK) and its relationship with clinicopathological parameters in laryngeal squamous cell carcinoma (LSCC). METHODS: 116 patients who had previously undergone complete resection of tumor for LSCC were studied retrospectively. The level of ILK expression in tumor tissues and adjacent nontumor tissues were determined by immunohistochemistry. RESULTS: Increased expression of ILK was found in 65.5% of cases. The expression of ILK protein was significantly associated with tumor grade (p=0.046), lymph node metastasis (p=0.020), and pTNM stage (p=0.019). Kaplan-Meier survival estimates showed a significant correlation between ILK expression and patient survival rate (log-rank p<0.05). The multivariate survival analysis revealed that N status was statistically significant prognostic factor (p<0.001). Other parameters, such as ILK expression, cannot predict disease prognosis separately. CONCLUSION: Increased expression of integrin-linked kinase is associated with lymph node metastases and patient survival rate in laryngeal squamous cell carcinoma. However, it does not appear to be an independent prognostic predictor in LSCC.

[Influences of different initial processing methods on Rheum palmatum].

OBJECTIVE: To choose the optimum initial processing methods of Rheum palmatum. METHODS: Fresh crude Rheum palmatum was sliced and dealt with the different drying methods such as sun drying, shady drying, microwave heating and various temperatures drying. The content of the Anthraquinones derivatives, slicing colors and dried rates were used as evaluation indexes. The sliced Rheum palmatum was compared with the traditional processing. RESULTS: Sliced fresh crude Rheum palmatum had the low content of the Anthraquinones derivatives and dry rates, slicing colours had obviously changes. For various drying methods, smoking drying was superior to sun drying, shady drying, microwave heating and various temperatures drying methods. CONCLUSION: Fresh crude Rheum palmatum is not suitable for slicing processing. The best drying method is smoking drying.

[Projecting from the superior olivary complex to the inner ear in the cat: a retrograde fluorescent labelling study].

OBJECTIVE: To investigate the distribution and projective feature of cat olivocochlear neurons. METHODS: Eleven adult cats were divided into two groups randomly. The experimental group of eight cats was injected of 1% cholera toxin B (CTB) to the left cochlea, while injected of 5% fluoro gold (FG) to the right cochlea. The control group of three cats was injected of saline to bilateral cochlea. After a survival time of 7 days, serial frozen sections were cut in the cat brainstem. All the sections were processed by immunofluorescent procedure for CTB and FG, and the labeled olivocochlear neurons were observed by fluorescent microscope. RESULTS: In the experimental group, the mean total of olivocochlear neurons labeled by CTB and FG was 3210 +/- 168, including lateral olivocochlear neurons (LOC, 2298 +/- 120) and medial olivocochlear neurons (MOC, 913 +/- 64). The labeled neurons were divided into three different types according to their feature of projection: neurons which only projected to the ipsilateral cochlea, neurons which only projected to the contralateral cochlea, and double-labeled neurons which projected both to the ipsilateral and contralateral cochlea, but the double-labeled neurons comprised 3.9% and 15.1% in the LOC and MOC system respectively. No labeled neurons were found in the control group. CONCLUSIONS: There are three types of neurons in the cat olivocochlear system. The neurons which projected to the bilateral cochlea may distribute both in the LOC and MOC system.

[Reconstruction with the anterolateral thigh flap interposition for defect after tumor resection of hypopharyngeal and cervical esophageal cancer].

OBJECTIVE: To evaluate the effectiveness of the anterolateral thigh flap in reconstruction for the tissue defects of hypopharyngeal and cervical esophageal tumor resection. METHOD: Retrospective review of two clinical cases who underwent pharyngoesophageal reconstruction with the anterolateral thigh flap after tumor ablation. RESULT: No flap failure, fistula and stricture occurred in two patients. Two patients tolerated a regular diet. An esophageal voice was progressively acquired with the help of speech therapy. With followup for 16 and 41 months two patients were alive without tumor evolution. CONCLUSION: The higher success rate,lower complication, quick recovery, made the anterolateral thigh flap interposition is the ideal choice for pharyngoesophageal reconstruction.

[Transmission disequilibrium test for nonsyndromic cleft lip and palate and segment homeobox gene-1 gene].

OBJECTIVE: To investigate the relationship between muscle segment homeobox gene-1 (MSX1) and the genetic susceptibility of nonsyndromic cleft lip and palate (NSCLP) in Hunan Hans. METHODS: One microsatellite DNA marker CA repeat in MSX1 intron region was used as genetic marker. The genotypes of 387 members in 129 NSCLP nuclear family trios were analyzed by polymerase chain reaction (PCR) and denaturing polyacrylamide gel electrophoresis. Then transmission disequilibrium test (TDT) and Logistic regression analysis were used to conduct association analysis. RESULTS: TDT analysis confirmed that CA4 allele in CL/P and CPO groups preferentially transmitted to the affected offspring (P = 0.018, P = 0.041). Logistic regression analysis indicated that the recessive model of inheritance was supported, and CA4 itself or CA4 acting as a marker for a disease allele or haplotype was inherited in a recessive fashion (P = 0.009). CONCLUSIONS: MSX1 gene is associated with NSCLP, and MSX1 gene may be directly involved either in the etiology of NSCLP or in linkage disequilibrium with disease-predisposing sites.

[Association study on microsatellite polymorphisms of MSX1 gene and nonsyndromic cleft lip and palate].

OBJECTIVE: To investigate muscle segment homeobox 1 (MSX1) microsatellite marker distribution and the relationship between MSX1 gene and the genetic susceptibility of nonsyndromic cleft lip and palate (NSCLP) in Hunan Hans. METHODS: One microsatellite DNA marker CA repeat in MSX1 intron region was used as genetic markers. The genotypes of 129 patients with NSCLP and 108 controls were analyzed by the techniques of polymerase chain reaction (PCR) and denaturing polyacrylamide gel electrophoresis (PAGE). Then case-control study was used to conduct association analysis. RESULTS: The allele frequencies of the CA repeat microsatellite DNA in Hunan Han normal population were in good agreement with Hardy-Weinberg equilibrium. The polymorphism information content and heterozygosity of CA repeat microsatellite DNA were 0.50 and 0.50 respectively. The allele CA4 frequency in CL/P and CPO group was significantly higher than that of normal controls (P<0.05). The genotype CA4,4 frequency was significantly higher in CL/P and CPO group than that in normal controls (P<0.05). CONCLUSION: The microsatellite DNA marker CA repeat in MSX1 is a good genetic marker. MSX1 gene is significantly associated with NSCLP in Hunan Hans.

[Association between retinoic acid receptor alpha gene polymorphisms and nonsyndromic cleft lip with or without cleft palate susceptibility].

OBJECTIVE: To investigate the relationship between D17S579 microsatellite marker allelic polymorphisms in retinoic acid receptor-alpha (RARA) gene and the genetic susceptibility to nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Hunan Hans. METHODS: PCR and denaturing polyacrylamide gel electrophoresis (PAGE) were used to detect the polymorphism of RARA gene marked by D17S579 among 140 patients with NSCL/P, 82 males and 58 females, aged 3 months-14 years, and 132 healthy persons, 68 males and 64 females, aged 6 months-14 years, who underwent physical examination. RESULTS: The A6 allele frequency of the NSCL/P patients was 8.93%, significantly higher than that of the healthy persons (4.17%, P = 0.026). The A9 allele frequency the NSCL/P patients was 13.21%, significantly higher than that of the healthy persons (5.68%, P = 0.003). There were not significant differences in the frequencies of different alleles between the patients with family history and the patients without family history (chi2 = 2.710, P = 0.978). CONCLUSION: The A6 and A9 alleles in D17S579 microsatellite marker of RARA gene may be correlated with the development of NSCL/P in Hunan Hans. There is no association between the family history and RARA polymorphism in the NSCL/P patients.

Clastogenic effect for cigarette smoking but not areca quid chewing as measured by micronuclei in exfoliated buccal mucosal cells.

The objective of this study was to use the micronuclei from exfoliated buccal mucosal cells to investigate the clastogenic effects of areca quid chewing and cigarette smoking, as well as the interaction between the two. The study population was selected from residents of seven villages recruited for a community-cohort study. A total of 141 subjects were recruited based on the regular consumption of cigarettes and betel quid. Salient personal characteristics were collected from interview using a specially designed questionnaire. Micronuclei were scored on Feulgen/fast green-stained smear preparations of exfoliated cells obtained by scraping the surface of the buccal mucosa. There was no significant interaction between the chewing of betel nut and cigarette smoking. Heavy smoking was positively associated with MN frequency, with areca quid chewing negatively associated. A significant positive trend was demonstrated for the relationship between MN frequency and either daily cigarette consumption or cumulative smoking pack-years. By contrast, negative trends were demonstrated for the analogous relationships with areca quid chewing. These results indicate that heavy smoking, but not areca quid chewing, increases MN formation. These findings suggest that the carcinogenesis of the oral cancers induced by areca quid chewing in Taiwan may be through a pathway other than genotoxicity.