Paddy soil geochemistry, uptake of trace elements by rice grains (Oryza sativa) and resulting health risks in the Mekong River Delta, Vietnam.

Soil geochemistry and phytoavailable trace elements were investigated in 80 paddy soil samples and corresponding rice grains from the Mekong River Delta in Vietnam. Soil parameters like Fe-, Al-, and Mn-phases, organic matter, and pH-value determine element concentrations in soil and affect their transfer into rice grains. Arsenic exceeded the allowed limit for Vietnamese agricultural soils in 11% of the samples, presumably caused by natural processes. Lead surpassed the limit in one soil sample. Other toxic elements were close to their natural concentrations and far below allowable limits for agricultural soil. There was no clear correlation of trace element concentrations in soils with those in corresponding grains, even if the different soil parameters and the large pH-range between 3.7 and 6.8 were considered. To assess health risks of critical elements in rice, the thresholds of tolerable upper intake level for total food and drinking water (UL) and of permissible maximum concentration (MC) for rice grains were evaluated. Surprisingly, rice grains grown on non- or low-polluted soils can surpass the upper limits. According to the UL concept, 12% of the grains exceeded the UL of As, 29% that of Cd, and 27% that of Pb for each gender. According to the MC concept, 5% of the rice grains exceeded the MC of inorganic As for adults and 38% that for young children. 24% of the grains surpassed the MC of Pb, while Cd in all grains was below the MC. The differing results of the UL and MC approaches show an urgent need for revision and harmonization concerning As, Cd, and Pb limits, especially regarding countries with high rice consumption.

Harmful and nutrient elements in paddy soils and their transfer into rice grains (Oryza sativa) along two river systems in northern and central Vietnam.

Thirty soil samples and 24 corresponding unpolished rice samples along the Red and Huong Rivers in northern and central Vietnam respectively, were analyzed in order to evaluate (a) soil geochemistry, (b) factors that determine the transfer of harmful and nutrient elements from soils into rice grains, (c) health risk to the local population through rice consumption. The concentrations of As, Bi, and U in the soils of this area are higher relative to those of average shale probably due to natural redox-related processes. Also, Zn, Ce, Th, La, Sn, Pb, and Cd are accumulated in some soils because of mining activities or industrial wastewater application. Arsenic concentrations exceed the Vietnamese allowable limit of 15 mg kg-1 in 80% of the tested soils. Twelve percent of the unpolished rice grains surpass the permissible maximum concentration of 0.2 mg Cd kg-1 grain dry matter by FAO/WHO and European Union, and all samples are below the Pb limit. The daily intake of As is within the range of the tolerable intake levels proposed by the European Food Safety Authority. Influences of soil parameters such as pH value, contents of soil organic matter, oxides/hydroxides of Al, Fe, and Mn cause a broad spread of transfer factors from soil to grains. Positive trends exist between the transfer factors within the groups (a) As, Sb, and U, (b) Co, Cu, Ni, and Zn, (c) Cd and Mn which indicate similar influences of soil parameters on their uptake. We propose that the allowable Cd maximum concentration for rice should be set to less than 0.2 mg kg-1. The analysis of As and Cd concentrations in soils and corresponding rice grains as well as the soil pH value should be made obligatory in order to prevent intoxication. In addition, critical elements from nonferrous metal mining and industrial areas should also be evaluated.

Tobacco retail availability and smoking-A systematic review and meta-analysis.

ISSUES: Health policy makers worldwide have adopted evidence-based legislation, largely directed at consumers, to reduce tobacco-related harm. It is suggested that limiting supply by decreasing retail availability can also reduce cigarette smoking. To inform policy makers this systematic literature review assesses whether reducing availability is associated with smoking behaviours. APPROACH: Systematic literature searches of five databases were carried out up to January 2023. Included studies had at least one exposure (tobacco retail density, proximity or mixed measures thereof) and outcomes of smoking behaviour. Meta-analysis of effect estimates were undertaken if there were at least three studies with similar population, exposure and outcome measures. KEY FINDINGS: Sixty-two studies were included, and positive associations were found between tobacco outlet density and cigarette smoking in pregnancy, youth, adults and cessation. Meta-analyses were undertaken for retail density and ever smoking (odds ratio [OR] 1.20; 95% confidence interval [CI] 1.04, 1.37; I2 = 87.3%), and current youth smoking (OR 1.23; 95% CI 1.08, 1.40; I2 = 0.0%), adult smoking (OR 1.11; 95% CI 1.01, 1.22; I2 = 74.8%); and mixed measures of retail availability near schools and current youth smoking (OR 1.03; 95% CI 1.01, 1.05; I2 = 0.0%). IMPLICATIONS AND CONCLUSION: There is evidence higher tobacco retail density is consistently associated with cigarette smoking in pregnant women, young people and adults when ecological studies are included in meta-analysis. Meanwhile, evidence synthesis reveals restrictive tobacco retail laws based on proximity or mixed measures near home or very near school may not reduce smoking except in men who smoke heavily. Mechanisms to reduce retailer density should be thus considered part of tobacco control strategies.

Distance education project of English idioms learning from watching YouTube.

Idioms have been recognized to be commonly adopted by academic practitioners in their speech and writing. However, despite their common occurrence in English communication, idioms pose great challenges for non-native English speakers, as they are often ignored in English classrooms. Particularly in Vietnam, a minimal number of idioms appear in English textbooks published by the Ministry of Education, and teachers appeared to under-emphasize English idioms' usefulness in conversation. To fill the gap, the present study adopted YouTube for Vietnamese students to undertake supplementary learning of English idiom knowledge. The study recruited 34 students and randomly assigned them to a control group and an experimental group. Both groups were required to take notes during their watching. Yet, only the experimental group would take extra exercises at the end of their watching. Immediate post-tests, delayed post-tests, and a survey were conducted. The findings demonstrate that the students in the two groups retained idiom knowledge similarly well. They were also positive towards learning English idioms through YouTube. Pedagogical implications and research suggestions are provided to conclude the study.

Assessment of availability, readiness, and challenges for scaling-up hypertension management services at primary healthcare facilities, Central Highland region, Vietnam, 2020.

INTRODUCTION: Vietnam aims for 95% of commune health stations (CHSs) to have functional hypertension management programs by 2025. However, limited resources may impede the Central Highland region health system from achieving this goal. We assessed the availability and readiness of hypertension management services at CHSs in the Central Highland region and identified challenges to facilitate evidence-based planning. METHODS: We used a mixed-methods cross-sectional design to assess hypertension management services using WHO's service availability and readiness assessment (SARA) tools in all 579 CHSs in the region, combined with twenty in-depth interviews of hypertension program focal points at communal, district, and provincial levels in all four provinces. We descriptively analyzed quantitative data and thematically analyzed qualitative data. RESULTS: Hypertension management services were available at 65% of CHSs, and the readiness of the services was 62%. The urban areas had higher availability and readiness indices in most domains (basic amenities, basic equipment, and essential medicines) compared to rural areas, except for staff and training. The qualitative results showed a lack of trained staff and ambiguity in national hypertension treatment guidelines, insufficient essential medicines supply mechanism, and low priority and funding limitations for the hypertension program. CONCLUSION: The overall availability and readiness for hypertension diagnosis and management service at CHSs in the Central Highland region were low, reflecting inadequate capacity of the primary healthcare facilities. Some measures to strengthen hypertension programs in the region might include increased financial support, ensuring a sufficient supply of basic medicines, and providing more specific treatment guidelines.

Reliability and validity of the Vietnamese version of the Hamilton D-17 scale.

Background: While depression is a common mental disorder, the diagnosis of this condition is still challenging. Thus, there is a need to have a validated tool to help evaluate symptoms of depression. This study aimed to evaluate the reliability and validity of the Vietnamese version of the Hamilton D-17 scale. Methods: A cross-sectional, descriptive, and validation study was conducted on 183 patients including 139 depressed and 44 non-depressed patients at the University Medical Center of Medicine and Pharmacy University at Ho Chi Minh City. Internal reliability and inter-rater reliability was measured using Cronbach's alpha and intraclass correlation coefficients (ICC). Confirmatory factor analysis (CFA) was used to evaluate construct validity. The Patient Health Questionnaire (PHQ9) was used to measure concurrent validity of the Hamilton D-17. Area under the ROC curve was used to measure criterion validity. Results: Both Cronbach alpha coefficient and ICC were at good level at alpha = 0.83 and ICC = 0.83. CFA with a second-order model consisting of four factors fitted the data at good to excellent level. The SRMR (Standardized Root Mean Squared Residual) was 0.066, RMSEA (Root Mean Square Error of Approximation) (90% CI) was 0.053 (0.036-0.069), CFI (comparative fit index) was 0.93, TLI (Tucker Lewis index) was 0.92. The Hamilton D-17 and the PHQ-9 had a correlation coefficient of r = 0.77 (p < 0.001). The Hamilton D-17 had a very high level of criterion validity with AUC of 0.93 (0.88-0.98). Conclusion: The Vietnamese version of the Hamilton D-17 scale has a high level of validity and reliability. The scale should be used to assess symptoms of depression among Vietnamese patients.

5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer.

BACKGROUND & AIMS: 5-Fluorouracil (5-FU)-based adjuvant chemotherapy does not increase survival times of patients with colorectal tumors with microsatellite instability. We determined the response of patients with colorectal tumors with the CpG island methylator phenotype (CIMP) to 5-FU-based therapy. METHODS: We analyzed a population-based cohort of 302 patients with colorectal cancer (CRC) for a median follow-up time of 50.7 months. CIMP status was determined by analysis of the CACNAG1, SOCS1, RUNX3, NEUROG1, and MLH1 promoters; tumors were considered to be CIMP positive if at least 3 promoters were methylated. RESULTS: Tumors from 29.5% of patients (89/302) were CIMP positive; CIMP status did not influence disease-free survival (DFS; log-rank = 0.3). Of tumors of TNM stages II-III (n = 196), 32.7% were CIMP positive. Among patients with stages II-III CRC who did not receive adjuvant 5-FU chemotherapy, those with CIMP-positive tumors had longest times of DFS (log-rank = 0.04); In patients who received chemotherapy, those with CIMP-positive tumors had shorter times of DFS (log-rank = 0.02). In patients with CIMP-negative tumors, adjuvant 5-FU chemotherapy significantly increased time of DFS (log-rank = 0.00001). However, in patients with CIMP-positive tumors, adjuvant 5-FU chemotherapy did not affect time of DFS (log-rank = 0.7). Multivariate analysis showed a significant, independent interaction between 5-FU treatment and CIMP status (hazard ratio [HR], 0.6; 95% confidence interval [CI], 0.5-0.8). Among patients with CIMP-positive tumors, adjuvant chemotherapy was not an independent predictor of outcome (HR, 0.8; 95% CI, 0.3-2.0). In patients who did not receive adjuvant 5-FU chemotherapy, CIMP status was the only independent predictor of survival (HR, 2.0; 95% CI, 1.1-3.8). CONCLUSIONS: Patients with CIMP-positive colorectal tumors do not benefit from 5-FU-based adjuvant chemotherapy.

Barriers and facilitators to more timely treatment of aneurysmal subarachnoid haemorrhage across two tertiary referral centres in Australia: A thematic analysis.

BACKGROUND: Delays in treatment of aSAH appear to be common but the causes are not well understood. We explored facilitators and barriers to timely treatment of aSAH. METHODS: We used a multiple case study with cases of aSAH surviving> 1 day identified prospectively. We conducted semi-structured interviews with the patient, their next-of-kin and health professionals involved in the case. Within-case analysis identified barriers and facilitators in 4 phases (pre-hospital, presentation, transfer, in-hospital) followed by thematic analysis across cases using a case-study matrix. RESULTS: Twenty-seven cases with 90 interviewees yielded five themes related to facilitators or barriers of timely treatment. "Early recognition" led to urgent response. "Accessibility to health care" depended on patient's location, transport, and environmental conditions. Good "Coordination" between and within health services was a key facilitator. "Complexity" of patient's condition affected time to treatment in multiple time periods. "Availability of resources" was identified most frequently during the diagnostic and treatment phases as both barrier and facilitator. CONCLUSIONS: The identified themes may be modifiable at the patient/health professional level and health system level and may improve timely treatment of aSAH through targeted interventions, subsequently contributing to improve morbidity and mortality of patients with aSAH.

De novo constitutional MLH1 epimutations confer early-onset colorectal cancer in two new sporadic Lynch syndrome cases, with derivation of the epimutation on the paternal allele in one.

Lynch syndrome is an autosomal dominant cancer predisposition syndrome classically caused by germline mutations of the mismatch repair genes, MLH1, MSH2, MSH6 and PMS2. Constitutional epimutations of the MLH1 gene, characterized by soma-wide methylation of a single allele of the promoter and allelic transcriptional silencing, have been identified in a subset of Lynch syndrome cases lacking a sequence mutation in MLH1. We report two individuals with no family history of colorectal cancer who developed that disease at age 18 and 20 years. In both cases, cancer had arisen because of the de novo occurrence of a constitutional MLH1 epimutation and somatic loss-of-heterozygosity of the functional allele in the tumors. We show for the first time that the epimutation in one case arose on the paternally inherited allele. Analysis of 13 tumors from seven individuals with constitutional MLH1 epimutations showed eight tumors had lost the second MLH1 allele, two tumors had a novel pathogenic missense mutation and three had retained heterozygosity. Only 1 of 12 tumors demonstrated the BRAF V600E mutation and 3 of 11 tumors harbored a mutation in KRAS. The finding that epimutations can originate on the paternal allele provides important new insights into the mechanism of origin of epimutations. It is clear that the second hit in MLH1 epimutation-associated tumors typically has a genetic not epigenetic basis. Individuals with mismatch repair-deficient cancers without the BRAF V600E mutation are candidates for germline screening for sequence or methylation changes in MLH1.

Aberrant DNA methylation in hereditary nonpolyposis colorectal cancer without mismatch repair deficiency.

BACKGROUND & AIMS: Approximately half of the families that fulfill Amsterdam criteria for Lynch syndrome or hereditary nonpolyposis colorectal cancer (HNPCC) do not have evidence of the germline mismatch repair gene mutations that define this syndrome and result in microsatellite instability (MSI). The carcinogenic pathways and the best diagnostic approaches to detect microsatellite stable (MSS) HNPCC tumors are unclear. We investigated the contribution of epigenetic alterations to the development of MSS HNPCC tumors. METHODS: Colorectal cancers were divided into 4 groups: (1) microsatellite stable, Amsterdam-positive (MSS HNPCC) (N = 22); (2) Lynch syndrome cancers (identified mismatch repair mutations) (N = 21); (3) sporadic MSS (N = 92); and (4) sporadic MSI (N = 46). Methylation status was evaluated for CACNAG1, SOCS1, RUNX3, NEUROG1, MLH1, and long interspersed nucleotide element-1 (LINE-1). KRAS and BRAF mutation status was analyzed. RESULTS: MSS HNPCC tumors displayed a significantly lower degree of LINE-1 methylation, a marker for global methylation, than any other group. Although most MSS HNPCC tumors had some degree of CpG island methylation, none presented a high index of methylation. MSS HNPCC tumors had KRAS mutations exclusively in codon 12, but none harbored V600E BRAF mutations. CONCLUSIONS: Tumors from Amsterdam-positive patients without mismatch repair deficiency (MSS HNPCC) have certain molecular features, including global hypomethylation, that distinguish them from all other colorectal cancers. These characteristics could have an important impact on tumor behavior or treatment response. Studies are underway to further assess the cause and effects of these features.

Identifying lower limb problems and the types of safety footwear worn in the Australian wine industry: a cross-sectional survey.

BACKGROUND: The Australian wine industry is a valuable part of the wider Australian economy worth approximately A$45 billion annually and employs 163,790 people either full time or part time. Australian agricultural industries are amongst the nation's most dangerous workplaces with joint, ligament, muscle and tendon injuries being commonplace along with wounds, lacerations and musculoskeletal diseases. It is therefore important to try and minimise the risk of injuries to workers. The aims of this study were to (1) identify whether lower limb problems occur in the Australian wine industry and (2) identify the types of safety footwear worn. METHODS: Participants were recruited from the Australian wine industry. The study was a cross-sectional anonymous survey of 82 questions with n = 207 respondents. Questions related to job role performed, types of lower limb problems experienced, level of pain, restriction of activities, types of footwear worn, general health and physical health. RESULTS: The main working roles were winery (73.4%), vineyard (52.2%), laboratory (39.6%), cellar door (32.4%) and office (8.2%), with 63.3% of participants working in more than one role. Lower back pain was the most commonly reported problem at 56% followed by foot pain (36.7%), knee pain (24.6%), leg pain (21.3%), ankle pain (17.9%), hip pain (15.5%), toe pain (13%) and heel pain (11.1%). The most popular footwear used by participants were elastic sided safety boots, followed by high cut lace up safety boots with side zip. Overall, although the pain experienced was moderate, it did not impact the workers ability to perform their duties and the majority self-reported as being in very good general and physical health. CONCLUSION: To date no data have been published on the types of lower limb problems or the types of safety footwear worn in the Australian wine industry. This study is the first to demonstrate that elastic sided safety boots were the most popular amongst respondents and that lower limb problems occur with workers. Therefore, further research into the safety footwear used in the Australian wine industry is needed to better support workers health while working in their varied roles and conditions.

An Evaluation of the Rabies Surveillance in Southern Vietnam.

Introduction: Rabies is endemic in Vietnam and has been a statutory notifiable infectious disease since 1998. We, herein, assessed the performance of rabies surveillance in Southern Vietnam and identified areas for improvement. Materials and Methods: We analyzed data on human rabies cases reported during 1991-2018. We adapted guidelines from the U.S. Centers for Disease Control and Prevention to evaluate attributes of surveillance. Between June and November 2018, we interviewed a total of 145 staff from hospitals, preventive medicine centers, and animal health offices at provincial and district levels in five southern provinces. Results: Between 2009 and 2018, an average of nine cases of human rabies (range: 4-20 cases) was reported annually in Southern Vietnam, representing an incidence of 2.7 cases per 10 million population. The highest incidence was observed in 2018 (5.5 cases per 10 million population). Survey data suggested that only 24% (13/53) of participants agreed that the monthly report template was easy to complete and that 42% (23/55) indicated that the change from the paper-based to the electronic case notification systems was easy. Only 7% (2/29) of human rabies cases were reported timely, and 65% (13/20) successfully collected specimens. Approximately 39% (56/144) of staff were aware of turning surveillance data into prevention activities, and 21% (31/145) witnessed data used for strategic program decision making. Conclusions: Although rabies surveillance was quite simple, flexible, and accepted in southern Vietnam, simplifying the report forms, training staff, and improving the timeliness of reporting and data usage are highly recommended for a better implementation of rabies surveillance.

The Contribution of Digital Health in the Response to Covid-19 in Vietnam.

Emerging from early of 2020, the COVID-19 pandemic has become one of the most serious health crisis globally. In response to such threat, a wide range of digital health applications has been deployed in Vietnam to strengthen surveillance, risk communication, diagnosis, and treatment of COVID-19. Digital health has brought enormous benefits to the fight against COVID-19, however, numerous constrains in digital health application remain. Lack of strong governance of digital health development and deployment; insufficient infrastructure and staff capacity for digital health application are among the main drawbacks. Despite several outstanding problems, digital health is expected to contribute to reducing the spread, improving the effectiveness of pandemic control, and adding to the dramatic transformation of the health system the post-COVID era.

Attributable Causes of Cancer in Vietnam.

PURPOSE: Vietnam is undergoing rapid socio-economic transition with an increasing cancer burden. The contribution of modifiable risk factors to cancers in Vietnam has not been studied. Therefore, we sought to evaluate the attributable causes of cancer in Vietnam. METHODS: We reviewed the data on burden of cancer in Vietnam from 2 cancer registries in Hanoi and Ho Chi Minh City between 1995 and 2012. Next, we calculated the fractions of cancers occurring in 2018 attributable to established modifiable risk factors whose impact could be quantified. Data on exposure prevalence were obtained for the period from 2000 to 2010 from national sources wherever possible. RESULTS: Cancer incidence in Vietnam has decreased slightly in both sexes. Cancer related to infectious agents decreased sharply, whereas cancer related to nutrition and metabolism has increased. In 2018, established carcinogens included in the analysis explained 47.0% of cancer burden in Vietnam. Chronic infections accounted for 29.1% of cancers (34.7% in men and 22.1% in women), tobacco smoking for 13.5% (23.9% in men and 0.8% in women), and alcohol drinking for 10.3%. Passive smoking was responsible for 8.8% of cancers in women. Other risk factors, including overweight or obesity, nulliparity, and low vegetable and fruit intake, accounted for < 1% of all cancers each. CONCLUSION: Cancer incidence is slowly decreasing in Vietnam, and the causes of more than half of cancers remain unexplained. This result underlines the need for further epidemiologic and fundamental research. Our findings confirm the notion that controlling oncogenic infections and decreasing tobacco smoking are the most effective approaches to reduce the burden of cancer in Vietnam, but other risk factors, including alcohol drinking and diet, should not be neglected.

Activation of CDK4 Triggers Development of Non-alcoholic Fatty Liver Disease.

The development of non-alcoholic fatty liver disease (NAFLD) is a multiple step process. Here, we show that activation of cdk4 triggers the development of NAFLD. We found that cdk4 protein levels are elevated in mouse models of NAFLD and in patients with fatty livers. This increase leads to C/EBPα phosphorylation on Ser193 and formation of C/EBPα-p300 complexes, resulting in hepatic steatosis, fibrosis, and hepatocellular carcinoma (HCC). The disruption of this pathway in cdk4-resistant C/EBPα-S193A mice dramatically reduces development of high-fat diet (HFD)-mediated NAFLD. In addition, inhibition of cdk4 by flavopiridol or PD-0332991 significantly reduces development of hepatic steatosis, the first step of NAFLD. Thus, this study reveals that activation of cdk4 triggers NAFLD and that inhibitors of cdk4 may be used for the prevention/treatment of NAFLD.

Microsatellite instability among individuals of Hispanic origin with colorectal cancer.

BACKGROUND: Although the presence of microsatellite instability (MSI) in patients with colorectal cancer (CRC) may have implications for prognosis, therapy, and family counseling, to the authors' knowledge, the prevalence of MSI has not been well described among individuals of Hispanic origin with CRC residing in the United States. METHODS: A retrospective cohort study using a hospital-based tumor registry to identify individuals of Hispanic origin who were diagnosed with CRC was conducted. Clinical data and tumor samples were retrieved. Molecular analyses included testing for MSI using a panel of 5 mononucleotide markers (BAT25, BAT26, NR21, NR24, and NR27) in a pentaplex polymerase chain reaction assay, as well as immunohistochemistry for the mismatch repair (MMR) proteins mutL homolog (MLH) 1, mutS homolog (MSH) 2, MSH6, and postmeiotic segregation increased 2 (PMS2) 2 on representative tissue. RESULTS: A total of 111 individuals of Hispanic origin with CRC were identified. Approximately 41.4% were women, and the median age was 57 years (interquartile range [IQR], 47.1-63.5 years). Eleven patients (9.9%; 95% confidence interval [95% CI], 4.2%-15.6%) had MSI CRC, whereas 14 patients (12.6%; 95% CI, 7.3%-21.8%) had CRC with ≥1 MMR protein abnormality. Ten of 11 individuals with MSI had clinical or molecular characteristics suspicious for Lynch syndrome such as abnormal expression of MSH2 and/or MSH6 (n=7) or age<50 years at the time of diagnosis (n=7). CONCLUSIONS: The prevalence of MSI CRC among Hispanic individuals may be similar to that of other races and ethnicities, but clinicopathological characteristics, including age at diagnosis and pattern of abnormal MMR protein expression, suggest that sporadic MSI CRC may be less common in individuals of Hispanic origin, and that much of the MSI observed in this situation may be attributable to Lynch syndrome. Further exploration of the causes of disparate presentations of CRC by ethnicity and race is warranted.

Genetic instability caused by loss of MutS homologue 3 in human colorectal cancer.

Microsatellite instability (MSI) is a hallmark of mismatch repair (MMR) deficiency. High levels of MSI at mononucleotide and dinucleotide repeats in colorectal cancer (CRC) are attributed to inactivation of the MMR genes, hMLH1 and hMSH2. CRC with low levels of MSI (MSI-L) exists; however, its molecular basis is unclear. There is another type of MSI--elevated microsatellite alterations at selected tetranucleotide repeats (EMAST)--where loci containing [AAAG](n) or [ATAG](n) repeats are unstable. EMAST is frequent in non-CRCs; however, the incidence of EMAST and its cause in CRC is not known. Here, we report that MutS homologue 3 (MSH3) knockdown or MSH3-deficient cells exhibit the EMAST phenotype and low levels of mutations at dinucleotide repeats. About 60% of 117 sporadic CRC cases exhibit EMAST. All of the cases defined as MSI-H (16 cases) exhibited high levels of EMAST. Among 101 non-MSI-H cases, all 19 cases of MSI-L and 35 of 82 cases of MSS exhibited EMAST. Although non-MSI-H CRC tissues contained MSH3-negative tumor cells ranging from 2% to 50% of the total tumor cell population, the tissues exhibiting EMAST contained more MSH3-negative cells (average, 31.5%) than did the tissues not exhibiting EMAST (8.4%). Taken together, our results support the concept that MSH3 deficiency causes EMAST or EMAST with low levels of MSI at loci with dinucleotide repeats in CRC.