A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

Association of green tea consumption with prediabetes, diabetes and markers of glucose metabolism in rural Vietnam: a cross-sectional study.

The literature on green tea consumption and glucose metabolism has reported conflicting findings. This cross-sectional study examined the association of green tea consumption with abnormal glucose metabolism among 3000 rural residents aged 40-60 years in Khánh Hòa province in Vietnam. Multinomial logistic regression analysis was conducted to examine the association of green tea consumption (0, < 200, 200-< 400, 400-< 600 or ≥ 600 ml/d) with prediabetes and diabetes (based on the American Diabetes Association criteria). Linear regression analysis was performed to examine the association between green tea consumption and the log-transformed homeostatic model assessment of insulin resistance (HOMA-IR) (a marker of insulin resistance) and the log-transformed homeostatic model assessment of ß-cell function (HOMA-ß) (a marker of insulin secretion). The OR for prediabetes and diabetes among participants who consumed ≥ 600 ml/d v. those who did not consume green tea were 1·61 (95 % CI = 1·07, 2·42) and 2·04 (95 % CI = 1·07, 3·89), respectively. Higher green tea consumption was associated with a higher level of log-transformed HOMA-IR (Pfor trend = 0·04) but not with a lower level of log-transformed HOMA-ß (Pfor trend = 0·75). Higher green tea consumption was positively associated with the prevalence of prediabetes, diabetes and insulin resistance in rural Vietnam. The findings of this study indicated prompting the need for further research considering context in understanding the link between green tea consumption and glucose metabolism, especially in rural settings in low- and middle-income countries.

Sex differences in the association between socioeconomic status and untreated hypertension among residents with hypertension in rural Khánh Hòa, Vietnam: a post-hoc analysis.

BACKGROUND: Several studies have examined the association between socioeconomic status (SES) and the proportion of untreated hypertension, but have produced conflicting findings. In addition, no study has been conducted to determine sex differences in the association between SES and untreated hypertension. Thus, the aim of this study was to examine whether the associations between SES and the proportion of untreated hypertension differed by sex in Vietnam. METHODS: This study was conducted using the data of 1189 individuals (558 males and 631 females) who were judged to have hypertension during the baseline survey of a prospective cohort study of 3000 residents aged 40-60 years in the Khánh Hòa Province. A multilevel Poisson regression model with a robust variance estimator was used to examine whether sex and SES indicators (household income and educational attainment) interacted in relation to untreated hypertension. RESULTS: The proportion of untreated hypertension among individuals identified as hypertensive was 69.1%. We found significant interaction between sex and SES indicators in relation to untreated hypertension (education: p < 0.001; household income: p < 0.001). Specifically, the association between SES and untreated hypertension was inverse among males while it was rather positive among females. CONCLUSIONS: Our finding suggests that the role of SES in the proportion of untreated hypertension might differ by sex.

Endoscopic Kyoto and Kimura-Takemoto Classifications Are Comparable in Predicting High-Risk Gastric Precancerous Lesions.

INTRODUCTION: Severe and extensive gastric atrophy, extensive or incomplete gastric intestinal metaplasia, and gastric dysplasia are considered high-risk gastric precancerous lesions (HGPLs). Endoscopic findings based on the endoscopic Kyoto classification (EKC) and the Kimura-Takemoto classification (KTC) have been reported to be significantly associated with HGPLs. This study aimed to compare these two classifications in predicting active Helicobacter pylori (H. pylori) infection and HGPLs. METHODS: This is a cross-sectional study conducted on naïve dyspeptic patients who underwent upper gastrointestinal endoscopy at a tertiary hospital. Endoscopic findings were scored according to the EKC and KTC. Mapping biopsies were taken, and H. pylori infection was determined using a locally validated rapid urease test and histology. The performance of EKC was compared with that of KTC using the area under the receiver operating characteristic curve (AUC) in predicting active H. pylori infection and HGPLs. RESULTS: There were 292 patients with a median age of 46 and a male-to-female ratio of 1:1. The rates of active H. pylori infection and HGPLs were 61.3% and 14.0%, respectively. The EKC was better than the KTC in predicting active H. pylori infection (AUC: 0.771 vs. 0.658, respectively; p < 0.001). However, these two classifications had comparable performance in predicting HGPLs (AUC: 0.792 vs. 0.791, respectively; p = 0.956). CONCLUSION: Compared to EKC, KTC is inferior in predicting active H. pylori infection but has comparable performance in predicting HGPLs.

Comparison of waist circumference and waist-to-height ratio as predictors of clustering of cardiovascular risk factors among middle-aged people in rural Khanh Hoa, Vietnam.

OBJECTIVE: Given the population-level variation in stature, a universal cut-off for waist circumference (WC) may not be appropriate for some populations. We compared the performance of WC and waist-to-height ratio (WHtR) to detect the clustering of cardiovascular disease (CVD) risk factors in rural Vietnam. METHODS: We obtained data from a baseline survey of the Khanh Hoa Cardiovascular Study comprising 2942 middle-aged residents (40-60 years). We used areas under the receiver operating characteristics curve (AUROC), net reclassification index (NRI), and integrated discrimination improvement (IDI) to compare the performance of WC and WHtR in predicting CVD risk clustering (≥2 of the following risk factors: hypertension, diabetes, dyslipidemia, and elevated C-reactive protein). RESULTS: The optimal cut-off values for WC were 81.8 and 80.7 cm for men and women, respectively. Regarding the clustering of CVD risk factors, the AUROC (95% CI) of WC and WHtR were 0.707 (0.676 to 0.739) and 0.719 (0.689 to 0.749) in men, and 0.682 (0.654 to 0.709) and 0.690 (0.663 to 0.717) in women, respectively. Compared with WC, WHtR had a better NRI (0.229; 0.102-0.344) and IDI (0.012; 0.004-0.020) in men and a better NRI (0.154; 0.050-0.257) in women. CONCLUSIONS: The optimal WC cut-off for Vietnamese men was approximately 10 cm below the recommended Asian cut-off. WHtR might perform slightly better in predicting the clustering of CVD risk factors among the rural population in Vietnam.

Association between Bacteroides fragilis and Fusobacterium nucleatum infection and colorectal cancer in Vietnamese patients.

BACKGROUND: Colorectal cancer (CRC) is a significant global health concern, and understanding the role of specific bacterial infections in its development and progression is of increasing interest. This cross-sectional study investigated the associations between Bacteroides fragilis (B. fragilis) and Fusobacterium nucleatum (F. nucleatum) infections and Vietnamese CRC patients. METHODS: 192 patients with either polyps or CRC at varying stages were recruited from May 2017 to December 2020. Real-time PCR assessed infection rates and bacterial loads in CRC tissues. RESULTS: B. fragilis infection was notably higher in CRC tissues (51.6 %) than polyps (9.4 %), with a fivefold higher relative load. Positive associations were found in stages II and III, indicating a fivefold increase in CRC progression risk. F. nucleatum infection rates were significantly higher in CRC tissues (55.2 %) than in polyps (10.5 %). In stage II, the infection rate exceeded that in adjacent tissues. The relative load of F. nucleatum was higher in stage III than in stages I and II. Positive F. nucleatum patients had a 3.2 times higher risk of CRC progression. CONCLUSION: These findings suggest associations between loading of F. nucleatum or/and B. fragilis with the advanced stages of CRC.

Enhancing powdery mildew resistance in soybean by targeted mutation of MLO genes using the CRISPR/Cas9 system.

BACKGROUND: Powdery mildew is a major disease that causes great losses in soybean yield and seed quality. Disease-resistant varieties, which are generated by reducing the impact of susceptibility genes through mutation in host plants, would be an effective approach to protect crops from this disease. The Mildew Locus O (MLO) genes are well-known susceptibility genes for powdery mildew in plant. In this study, we utilized the CRISPR/Cas9 system to induce targeted mutations in the soybean GmMLO genes to improve powdery mildew resistance. RESULTS: A dual-sgRNA CRISPR/Cas9 construct was designed and successfully transferred into the Vietnamese soybean cultivar DT26 through Agrobacterium tumefaciens-mediated transformation. Various mutant forms of the GmMLO genes including biallelic, chimeric and homozygous were found at the T0 generation. The inheritance and segregation of CRISPR/Cas9-induced mutations were confirmed and validated at the T1 and T2 generations. Out of six GmMLO genes in the soybean genome, we obtained the Gmmlo02/Gmmlo19/Gmmlo23 triple and Gmmlo02/Gmmlo19/Gmmlo20/Gmmlo23 quadruple knockout mutants at the T2 generation. When challenged with Erysiphe diffusa, a fungus that causes soybean powdery mildew, all mutant plants showed enhanced resistance to the pathogen, especially the quadruple mutant. The powdery mildew severity in the mutant soybeans was reduced by up to 36.4% compared to wild-type plants. In addition, no pleiotropic effect on soybean growth and development under net-house conditions was observed in the CRISPR/Cas9 mutants. CONCLUSIONS: Our results indicate the involvement of GmMLO02, GmMLO19, GmMLO20 and GmMLO23 genes in powdery mildew susceptibility in soybean. Further research should be conducted to investigate the roles of individual tested genes and the involvement of other GmMLO genes in this disease infection mechanism. Importantly, utilizing the CRISPR/Cas9 system successfully created the Gmmlo transgene-free homozygous mutant lines with enhanced resistance to powdery mildew, which could be potential materials for soybean breeding programs.

An EZH2-dependent transcriptional complex promotes aberrant epithelial remodelling after injury.

Unveiling the molecular mechanisms of tissue remodelling following injury is imperative to elucidate its regenerative capacity and aberrant repair in disease. Using different omics approaches, we identified enhancer of zester homolog 2 (EZH2) as a key regulator of fibrosis in injured lung epithelium. Epithelial injury drives an enrichment of nuclear transforming growth factor-ß-activated kinase 1 (TAK1) that mediates EZH2 phosphorylation to facilitate its liberation from polycomb repressive complex 2 (PRC2). This process results in the establishment of a transcriptional complex of EZH2, RNA-polymerase II (POL2) and nuclear actin, which orchestrates aberrant epithelial repair programmes. The liberation of EZH2 from PRC2 is accompanied by an EZH2-EZH1 switch to preserve H3K27me3 deposition at non-target genes. Loss of epithelial TAK1, EZH2 or blocking nuclear actin influx attenuates the fibrotic cascade and restores respiratory homeostasis. Accordingly, EZH2 inhibition significantly improves outcomes in a pulmonary fibrosis mouse model. Our results reveal an important non-canonical function of EZH2, paving the way for new therapeutic interventions in fibrotic lung diseases.

Parental absence during childhood and weight status in adulthood among middle-aged community dwellers in rural Vietnam.

OBJECTIVES: While adverse childhood experiences (ACEs) have been shown to be associated with adulthood obesity, less is known about their association with underweight. We examined the associations between parental absence (i.e., a major component of ACEs) and both underweight and excess weight among middle-aged rural community dwellers in Vietnam, where experiences of parental absence was not uncommon during and after the Vietnam War (1955-1975). METHODS: Data came from 3000 middle-aged adults who participated in the baseline survey of Khánh Hòa Cardiovascular Study. Parental absence was defined as parental absence due to death, divorce, or out-migration. Using information on the timing of such events, we categorized participants into those who experienced parental absence before the age of 3, between the ages of 3 and 15, and those without such experiences. BMI was calculated based on measured height and weight (kg/m2 ) and categorized into three groups: underweight <18.5; normal 18.5-24.9; excess weight ≥ 25. Multinomial logistic regression was then used to investigate the association between parental absence and adult weight status. RESULTS: Parental absence that occurred before the age of 3 was marginally significantly associated with underweight (relative risk ratio [RRR] = 1.44, 95% confidence interval [CI] 0.95, 2.20) but not with overweight/obesity. Parental divorce was associated with overweight/obesity (RRR = 2.48, 95% CI 1.28, 4.81), but not parental absence due to migratory work. CONCLUSIONS: While previous studies in Western settings focused almost exclusively on the risk of obesity in relation to exposure to ACEs, our findings point to the potential importance of considering the risk of underweight in low- and middle-income countries.

Red meat consumption is associated with prediabetes and diabetes in rural Vietnam: a cross-sectional study.

OBJECTIVE: To examine the association between red/processed meat consumption and glycaemic conditions (i.e. prediabetes (preDM) and diabetes mellitus (DM)) among middle-aged residents in rural Khánh Hòa, Vietnam. DESIGN: In this cross-sectional study, a multinomial logistic regression model was used to examine the association between daily consumption of red/processed meat (0-99 g, 100-199 g or ≥ 200 g) and preDM/DM with adjustments for socio-demographic, lifestyle-related and health-related variables. SETTING: Khánh Hòa Province, Vietnam. PARTICIPANTS: The study used data collected through a baseline survey conducted during a prospective cohort study on CVD among 3000 residents, aged 40-60 years, living in rural communes in Khánh Hòa Province. RESULTS: The multinomial regression model revealed that the relative-risk ratios for DM were 1·00 (reference), 1·11 (95 % CI = 0·75, 1·62) and 1·80 (95 % CI = 1·40, 2·32) from the lowest to the highest red/processed meat consumption categories (Ptrend = 0·006). The corresponding values for preDM were 1·00 (reference), 1·25 (95 % CI = 1·01, 1·54) and 1·67 (95 % CI = 1·20, 2·33) (Ptrend = 0·004). We did not find any evidence of statistical significance in relation to poultry consumption. CONCLUSION: Increased red/processed meat consumption, but not poultry consumption, was positively associated with the prevalence of preDM/DM in rural communes in Khánh Hòa Province, Vietnam. Dietary recommendations involving a reduction in red/processed meat consumption should be considered in low- and middle-income countries.

Eating speed and abdominal adiposity in middle-aged adults: a cross-sectional study in Vietnam.

BACKGROUND: Several studies have associated fast eating speed with the risk of general obesity, but there are inadequate data on the association between eating speed and abdominal adiposity which may pose a higher threat to health than general obesity. The present study aimed to investigate the association between eating speed and abdominal obesity in a Vietnamese population. METHODS: Between June 2019 and June 2020, the baseline survey of an ongoing prospective cohort study on the determinants of cardiovascular disease in Vietnamese adults was conducted. A total of 3,000 people aged 40-60 years old (1,160 men and 1,840 women) were recruited from eight communes in the rural district of Cam Lam, Khanh Hoa province, in Central Vietnam. Self-reported eating speed was assessed on a 5-point Likert scale, and responses were collapsed into the following three categories: slow, normal, and fast. Abdominal obesity was defined as a waist-to-height ratio of ≥ 0.5. Poisson regression with a robust variance estimator was used to assess the association between eating speed and abdominal obesity. RESULTS: Compared with slow eating speed, the adjusted prevalence ratio (95% confidence interval) for abdominal obesity was 1.14 (1.05, 1.25)1.14 (1.05, 1.25) for normal eating speed and 1.30 (1.19, 1.41) for fast eating speed (P for trend < 0.001). CONCLUSION: A faster eating speed was associated with a higher prevalence of abdominal obesity in a middle-aged population in rural Vietnam.

Different associations of occupational and leisure-time physical activity with the prevalence of hypertension among middle-aged community dwellers in rural Khánh Hòa, Vietnam.

BACKGROUND: In contrast to high-income countries where physical activity (PA), particularly leisure-time PA, has been shown to be protective against hypertension, few studies have been conducted in low- and middle-income countries. We examined the cross-sectional association between PA and hypertension prevalence among rural residents in Vietnam. METHODS: We used data collected in the baseline survey of a prospective cohort study, among 3000 people aged 40-60 years old residing in rural Khánh Hòa, Vietnam. Hypertension was defined as systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, or the use of antihypertensive medication. We assessed occupational PA and leisure-time PA using the Global Physical Activity Questionnaire. A robust Poisson regression model was used to investigate the associations, with adjustment for covariates. RESULTS: The prevalence of hypertension was 39.6%. After adjusting for socio-demographic and lifestyle-related variables, leisure-time PA was positively associated with hypertension prevalence (prevalence ratio [PR]: 1.03 per 10 MET-hour/week, 95% confidence interval [CI] 1.01-1.06). Occupational PA was inversely associated with hypertension prevalence (PR: 0.98 per 50 MET-hour/week, 95% CI = 0.96-0.996). After adjusting for BMI and other health-related variables, the association related to occupational PA became statistically non-significant, while the association related to leisure-time PA remained statistically significant. CONCLUSION: In contrast to previous studies in high-income countries, we found that leisure-time PA was positively associated with hypertension prevalence and occupational PA was associated with a lower hypertension prevalence. This suggests that the association between PA and hypertension might differ depending on the context.

Compact UHF Circularly Polarized Multi-Band Quadrifilar Antenna for CubeSat.

This article presents a multi-band right-hand circularly polarized antenna designed for the Cube Satellite (CubeSat). Based on a quadrifilar structure, the antenna provides circular polarization radiation suitable for satellite communication. Moreover, the antenna is designed and fabricated using two 1.6 mm thickness FR4-Epoxy boards connected by metal pins. In order to improve the robustness, a ceramic spacer is placed in the centerboard, and four screws are added at the corners to fix the antenna to the CubeSat structure. These additional parts reduce antenna damage caused by vibrations in the launch vehicle lift-off stage. The proposal has a dimension of 77 × 77 × 10 mm3 and covers the LoRa frequency bands at 868 MHz, 915 MHz, and 923 MHz. According to the measurements in the anechoic chamber, antenna gains with the values of 2.3 dBic and 1.1 dBic are obtained for the 870 MHz and 920 MHz, respectively. Finally, the antenna is integrated into a 3U CubeSat that was launched by a Soyuz launch vehicle in September 2020. The terrestrial-to-space communication link was measured, and the antenna performance was confirmed in a real-life scenario.

Youth-centered Recommendations to Address Social Stigma and Discrimination Against Unhoused Youth: An Integrative Literature Review.

Youth between ages 13 and 25 who experience homelessness face numerous barriers to excellent health, including social stigma and discrimination. Applying socio-ecological model and intersectionality theory, an integrative literature review was conducted. Peer-reviewed studies (N = 29) representing 808,296 participants extracted from four databases (CINAHL, MEDLINE, PsychINFO, SocINDEX) were analyzed. The studies included sources of discrimination and stigma from interpersonal interactions with support services staff upwards to policy and systemic levels with housing and justice systems. Health outcomes include poorer physical and behavioral health status from increased likeliness of denied access to support services, prolonged time spent being homeless, and higher incidences of experiencing violence. School nursing has power to push for recommended changes and support unhoused youth towards excellent health. Proposed changes include adapting Housing First framework, engaging with unhoused youth in program planning, policy writing, and public education that address the causes of poverty.

Cassava mosaic disease and its management in Southeast Asia.

KEY MESSAGE: Status of the current outbreak of cassava mosaic disease (CMD) in Southeast Asia was reviewed. Healthy cassava seed production and dissemination systems have been established in Vietnam and Cambodia, along with integrated disease and pest management systems, to combat the outbreak. Cassava (Manihot esculenta Crantz) is one of the most important edible crops in tropical and subtropical regions. Recently, invasive insect pests and diseases have resulted in serious losses to cassava in Southeast Asia. In this review we discuss the current outbreak of cassava mosaic disease (CMD) caused by the Sri Lankan cassava mosaic virus (SLCMV) in Southeast Asia, and summarize similarities between SLCMV and other cassava mosaic begomoviruses. A SATREPS (Science and Technology Research Partnership for Sustainable Development) project "Development and dissemination of sustainable production systems based on invasive pest management of cassava in Vietnam, Cambodia and Thailand", was launched in 2016, which has been funded by The Japan International Cooperation Agency (JICA) and The Japan Science and Technology Agency (JST), Japan. The objectives of SATREPS were to establish healthy seed production and dissemination systems for cassava in south Vietnam and Cambodia, and to develop management systems for plant diseases and insect pests of cassava. To achieve these goals, model systems of healthy seed production in Vietnam and Cambodia have been developed incorporating CMD-resistant planting materials through international networks with The International Center for Tropical Agriculture (CIAT) and The International Institute of Tropical Agriculture (IITA).

Field transcriptome analysis reveals a molecular mechanism for cassava-flowering in a mountainous environment in Southeast Asia.

KEY MESSAGE: The field survey in this article showed in 'KU50', a popular variety and late-branching type of cassava in Southeast Asia, that flowering rarely occurs in normal-field conditions in Southeast Asia but is strongly induced in the dry season in the mountainous region. Flowering time is correlated with the expression patterns of MeFT1 and homologs of Arabidopsis GI, PHYA, and NF-Ys. Cassava (Manihot esculenta Crantz) is a tropical crop that is propagated vegetatively rather than sexually by seed. Flowering rarely occurs in the erect-type variety grown in Southeast Asia, but it is known that cassava produces flowers every year in mountainous regions. Data pertaining to the effect of environmental factors on flowering time and gene expression in cassava, however, is limited. The aim of the present study was to determine the kinds of environmental conditions that regulate flowering time in cassava and the underlying molecular mechanisms. The flowering status of KU50, a popular variety in Southeast Asia and late-branching type of cassava, was monitored in six fields in Vietnam and Cambodia. At non-flowering and flowering field locations in North Vietnam, the two FLOWERING LOCUS T (FT)-like genes, MeFT1 and MeFT2, were characterized by qPCR, and the pattern of expression of flowering-related genes and genes responsive to environmental signals were analyzed by using RNA sequencing data from time-series samples. Results indicate that cassava flowering was induced in the dry season in the mountain region, and that flowering time was correlated with the expression of MeFT1, and homologs of Arabidopsis GI, PHYA, and NF-Ys. Based upon these data, we hypothesize that floral induction in cassava is triggered by some conditions present in the mountain regions during the dry season.

The antimicrobial peptide S100A8/A9 produced by airway epithelium functions as a potent and direct regulator of macrophage phenotype and function.

BACKGROUND: Elevated counts of alveolar macrophages and attenuated phagocytic capacity are associated with chronic obstructive pulmonary disease (COPD). Factors governing macrophage phagocytosis are poorly understood. In this study we aimed to compare the influence of airway epithelial cell secretions from individuals with COPD and without COPD (non-COPD) on macrophage phagocytic activity, and the role of antimicrobial peptides (AMPs). METHODS: Supernatants from non-COPD and COPD small airway epithelial cell (SAEC) cultures exposed to non-typeable Haemophilus influenzae (NTHi) were applied to human monocyte-derived macrophages (MDMs) to assess their influence on phagocytosis. SAECs were analysed for changes in AMP expression by quantitative reverse transcription PCR, and the influence of select AMPs on macrophage phenotype and function was assessed by flow cytometry and metabolic activity assay. RESULTS: Secretions from the apical and basolateral surface of NTHi-exposed SAECs from non-COPD donors elicited superior phagocytic capacity in MDMs. Moreover, NTHi exposure led to a rapid increase in the expression of a range of AMPs by non-COPD SAECs, but this response was delayed in COPD SAECs. We demonstrate that treatment with AMPs ß-defensin 2 and S100 calcium binding protein A8/S100 calcium binding protein A9 (S100A8/A9) improved the phagocytic capacity of MDMs. In-depth analysis of the influence of S100A8/A9 on MDMs revealed a role for this AMP in macrophage phenotype and function. Furthermore, we show that the expression of S100A8 and S100A9 is directly regulated by WNT/ß-catenin signalling, a known deregulated pathway in COPD. CONCLUSION: In conclusion, for the first time, we demonstrate that airway epithelium from patients with COPD has a reduced capacity to support the phagocytic function of macrophages in response to acute NTHi exposure, and we identify the WNT/ß-catenin signalling-modulated and epithelium-derived S100A8/A9 as a potent regulator of macrophage phenotype and function.

Performance of chromoendoscopy and narrow-band imaging in the diagnosis of gastric intestinal metaplasia.

BACKGROUND/AIMS: Chromoendoscopy and narrow-band imaging (NBI) have been reported to aid in the diagnosis of gastric intestinal metaplasia (GIM). This study aimed to assess the diagnostic validity of chromoendoscopy combined with NBI in the diagnosis of GIM in Vietnamese. METHODS: A cross-sectional study was carried out on patients with dyspeptic symptoms who underwent esophagogastroduodenoscopy (EGD) at the University Medical Center at Ho Chi Minh City. We compared the detection rates of GIM in the group of patients examined with white-light endoscopy (WLE) alone and those examined with WLE in combination with chromoendoscopy and NBI. RESULTS: A total of 374 patients have been recruited. The additional GIM detection rate after chromoendoscopy combined with NBI was 8.6% (95% confidence interval [CI]: 4.3 - 12.8), p < .005. The rate of GIM within the group of patients biopsied under the guidance of chromoendoscopy combined with NBI was statistically significantly higher than in the group with WLE alone with a distinct rate of 14.4% (95% CI: 6.3 - 2.6), p = .001. CONCLUSIONS: Chromoendoscopy combined with NBI helped to detect the GIM lesions missed by WLE and was a more reliable endoscopic method for the diagnosis of GIM.

Effects of autophagy inhibition by chloroquine on hepatic stellate cell activation in CCl4-induced acute liver injury mouse model.

BACKGROUND AND AIM: Hepatic stellate cells (HSCs) activation, a critical event in liver fibrosis, has been recently shown to be related to autophagy. Determine whether chloroquine (CQ) could affect (i) the activation of HSC in vivo and (ii) the hepatic damage in a mice acute liver injury model. METHODS: The acute liver injury was induced in BALB/c mice by carbon tetrachloride (CCl4 group); 24 h before and after CCl4 administration animals were treated by CQ (CCl4  + CQ group). As control, mice treated by olive oil were considered. After 48 h from CCl4 /olive oil administration, blood samples, liver tissues, and HSCs were harvested for analysis. RESULTS: In vivo, CQ attenuates CCl4 -induced acute liver damage as evidenced by (i) the reduction of liver enlargement, (ii) the reduction of liver swelling and necrosis also supported by a certain decrease of circulating transaminases level, and (iii) the reduction of liver fibrosis evaluated by collagen deposition and α-sma protein expression. In HSCs isolated from CQ treated group, we observed the inhibition of autophagy proved by the increase in p62 protein and the decrease of lc3 protein. In addition, CQ reduced the expression of the HSCs activation markers α-sma/collagen-I and down-regulated the expression of the proliferative marker ki67. CONCLUSION: The autophagy attenuation exerted by CQ together with the reduction of the expression of the proliferation marker in HSCs can lessen the acute liver damage potentially opening the way to novel therapeutic approaches for hepatic fibrosis.

First report of foodborne botulism due to Clostridium botulinum type A(B) from vegetarian home-canned pate in Hanoi, Vietnam.

Even one case of foodborne botulism constitutes a public health emergency. We report a series of cases with delayed treatment due to delayed diagnosis. Clostridium botulinum type A(B) was isolated from vegetarian home-canned pate, but not from stool samples. These are the first recorded cases of foodborne botulism in Hanoi.