The T1150A cancer mutant of the protein lysine dimethyltransferase NSD2 can introduce H3K36 trimethylation.

Protein lysine methyltransferases (PKMTs) play essential roles in gene expression regulation and cancer development. Somatic mutations in PKMTs are frequently observed in cancer cells. In biochemical experiments, we show here that the NSD1 mutations Y1971C, R2017Q, and R2017L observed mostly in solid cancers are catalytically inactive suggesting that NSD1 acts as a tumor suppressor gene in these tumors. In contrast, the frequently observed T1150A in NSD2 and its T2029A counterpart in NSD1, both observed in leukemia, are hyperactive and introduce up to three methyl groups in H3K36 in biochemical and cellular assays, while wildtype NSD2 and NSD1 only introduce up to two methyl groups. In Molecular Dynamics simulations, we determined key mechanistic and structural features controlling the product specificity of this class of enzymes. Simulations with NSD2 revealed that H3K36me3 formation is possible due to an enlarged active site pocket of T1150A and loss of direct contacts of T1150 to critical residues which regulate the product specificity of NSD2. Bioinformatic analyses of published data suggested that the generation of H3K36me3 by NSD2 T1150A could alter gene regulation by antagonizing H3K27me3 finally leading to the upregulation of oncogenes.

Accuracy of cuff blood pressure and systolic blood pressure amplification.

Automated cuff measured blood pressure (BP) is the global standard used for diagnosing hypertension, but there are concerns regarding the accuracy of the method. Individual variability in systolic BP (SBP) amplification from central (aorta) to peripheral (brachial) arteries could be related to the accuracy of cuff BP, but this has never been determined and was the aim of this study. Automated cuff BP and invasive brachial BP were recorded in 795 participants (74% male, aged 64 ± 11 years) receiving coronary angiography at five independent research sites (using seven different automated cuff BP devices). SBP amplification was recorded invasively by catheter and defined as brachial SBP minus aortic SBP. Compared with invasive brachial SBP, cuff SBP was significantly underestimated (130 ± 18 mmHg vs. 138 ± 22 mmHg, p < 0.001). The level of SBP amplification varied significantly among individuals (mean ± SD, 7.3 ± 9.1 mmHg) and was similar to level of difference between cuff and invasive brachial SBP (mean difference -7.6 ± 11.9 mmHg). SBP amplification explained most of the variance in accuracy of cuff SBP (R2 = 19%). The accuracy of cuff SBP was greatest among participants with the lowest SBP amplification (ptrend < 0.001). After cuff BP values were corrected for SBP amplification, there was a significant improvement in the mean difference from the intra-arterial standard (p < 0.0001) and in the accuracy of hypertension classification according to 2017 ACC/AHA guideline thresholds (p = 0.005). The level of SBP amplification is a critical factor associated with the accuracy of conventional automated cuff measured BP.

Comparison between cuff-based and invasive systolic blood pressure amplification.

OBJECTIVE: Accurate measurement of central blood pressure (BP) using upper arm cuff-based methods is associated with several factors, including determining the level of systolic BP (SBP) amplification. This study aimed to determine the agreement between cuff-based and invasively measured SBP amplification. METHODS: Patients undergoing coronary angiography had invasive SBP amplification (brachial SBP - central SBP) measured simultaneously with cuff-based SBP amplification using a commercially available central BP device (device 1: Sphygmocor Xcel; n = 171, 70% men, 60 ±â€Š10 years) and a now superseded model of a central BP device (device 2: Uscom BP+; n = 52, 83% men, 62 ±â€Š10 years). RESULTS: Mean difference (±2SD, limits of agreement) between cuff-based and invasive SBP amplification was 4 mmHg (-12, +20 mmHg, P < 0.001) for device 1 and -2 mmHg (-14, +10 mmHg, P = 0.10) for device 2. Both devices systematically overestimated SBP amplification at lower levels and underestimated at higher levels of invasive SBP amplification, but with stronger bias for device 1 (r = -0.68 vs. r = -0.52; Z = 2.72; P = 0.008). Concordance of cuff-based and invasive SBP amplification across quartiles of invasive SBP amplification was low, particularly in the lowest and highest quartiles. The root mean square errors from regression between cuff-based central SBP and brachial SBP were significantly lower (indicating less variability) than from invasive regression models (P < 0.001). CONCLUSIONS: Irrespective of the difference from invasive measurements, cuff-based estimates of SBP amplification showed evidence of proportional systematic bias and had less individual variability. These observations could provide insights on how to improve the performance of cuff-based central BP.

Ferroelectric PVDF nanofiber membrane for high-efficiency PM0.3 air filtration with low air flow resistance.

The significant public health concerns related to particulate matter (PM) air pollutants and the airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to considerable interest in high-performance air filtration membranes. Highly ferroelectric polyvinylidene fluoride (PVDF) nanofiber (NF) filter membranes are successfully fabricated via electrospinning for high-performance low-cost air filtration. Spectroscopic and ferro-/piezoelectric analyses of PVDF NF show that a thinner PVDF NF typically forms a ferroelectric ß phase with a confinement effect. A 70-nm PVDF NF membrane exhibits the highest fraction of ß phase (87%) and the largest polarization behavior from piezoresponse force microscopy. An ultrathin 70-nm PVDF NF membrane exhibits a high PM0.3 filtration efficiency of 97.40% with a low pressure drop of 51 Pa at an air flow of 5.3 cm/s owing to the synergetic combination of the slip effect and ferroelectric dipole interaction. Additionally, the 70-nm PVDF NF membrane shows excellent thermal and chemical stabilities with negligible filtration performance degradation (air filtration efficiency of 95.99% and 87.90% and pressure drop of 55 and 65 Pa, respectively) after 24 h of heating at 120 °C and 1 h immersion in isopropanol.

Sex differences in total cholesterol of Vietnamese adults.

BACKGROUND: The mid-life emergence of higher levels of total cholesterol (TC) for women than for men has been observed in different Western and Asian populations. The aim of this study was to investigate whether there is evidence of this in Vietnam and, if so, whether it can be explained by ageing, by body size and fatness, or by socio-demographic characteristics and behavioural factors. METHODS: Participants (n = 14706, 50.9% females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Linear regression was used to assess the independent contributions of potential explanatory factors to mean levels of TC. Data were analysed using complex survey methods. RESULTS: Men and women had similar mean levels of body mass index (BMI), and men had modestly higher mean levels of waist circumference (WC), in each 5-year age category. The mean TC of women increased more or less continuously across the age range but with a step-up at age 50 years to reach higher concentrations on average than those of their male counterparts. The estimated step-up was not eliminated by adjustment for anthropometric indices including BMI or WC, or by adjustment for socio-demographic characteristics or behavioural factors. The estimated step-up was least for women with the greatest weight. CONCLUSION: There is a marked step-up in TC at age 50 years for Vietnamese women that cannot be explained by their age, or by their body fatness or its distribution, or by their socio-demographic characteristics or behavioural factors, and which results in greater mean levels of TC for middle-aged women than for their male counterparts in Vietnam.

A highly efficient nanofibrous air filter membrane fabricated using electrospun amphiphilic PVDF-g-POEM double comb copolymer.

Current global emergencies, such as the COVID-19 pandemic and particulate matter (PM) pollution, require urgent protective measures. Nanofibrous air filter membranes that can capture PM0.3 and simultaneously help in preventing the spread of COVID-19 are essential. Therefore, a highly efficient nanofibrous air filter membrane based on amphiphilic poly(vinylidene fluoride)-graft-poly(oxyethylene methacrylate) (PVDF-g-POEM) double comb copolymer was fabricated using atomic transfer radical polymerization (ATRP) and electrospinning. Fourier transform infrared spectroscopy, X-ray diffraction, proton nuclear magnetic resonance, transmission electron microscopy, differential scanning calorimetry, and thermogravimetric analysis were employed to successfully characterize the molecular structure of the fabricated amphiphilic PVDF-g-POEM double comb copolymer. The nanofibrous air filter membrane based on amphiphilic PVDF-g-POEM double comb copolymer achieved a low air resistance of 4.69 mm H2O and a high filtration efficiency of 93.56 % due to enhanced chemical and physical adsorption properties.

Misclassification of blood pressure of Vietnamese adults when only a single measurement is used.

A single clinic measurement of blood pressure (BP) may be common in low- and middle-income countries because of limited medical resources. This study aimed to examine the potential misclassification error when only one BP measurement is used. Participants (n = 14,706, 53.5% females) aged 25-64 years were selected by multistage stratified cluster sampling from eight provinces, each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Data were analyzed using complex survey methods. For systolic BP, 62.7% had a higher first reading whereas 30.0% had a lower first reading, and 27.3% had a reduction of at least 5 mmHg whereas 9.6% had an increase of at least 5 mmHg. Irrespective of direction of change, increased variability in BP was associated with greater age, urban living, greater body size and fatness, reduced physical activity levels, elevated glucose, and raised total cholesterol. These measurement variations would lead to substantial misclassification in diagnosis of hypertension based on a single reading because almost 20% of subjects would receive a different diagnosis based on the mean of two readings.

The importance of waist circumference and body mass index in cross-sectional relationships with risk of cardiovascular disease in Vietnam.

BACKGROUND: Waist circumference (WC) is an indicator of intra-abdominal adipose tissue, high levels of which confer an increased risk of cardiometabolic disease. Population data on WC should be more informative than data on body mass index (BMI), which is a general indicator of body size. This study aimed to evaluate the importance of WC relative to BMI in cross-sectional relationships with blood pressure (BP), glucose, and total cholesterol (TC) in the adult population of Vietnam. METHODS: The data were collected in a population-based survey conducted during 2009-10 using the "WHO STEPwise approach to surveillance of risk factors for non-communicable disease" (STEPS) methodology. The survey participants (n = 14 706 aged 25 to 64 years) were selected by multi-stage stratified cluster sampling from eight provinces representative of the eight geographical regions of Vietnam. All measurements were performed in accordance with the STEPS protocols. All analyses were performed using complex survey methods. RESULTS: The measurements of WC and BMI were highly correlated (men r = 0.80, women r = 0.77). For men, the strongest and predominant associations with BP, glucose, and TC were for WC or an index based on WC. For women, this was true for glucose but BMI was more important for BP and TC. WC or an index based on WC provided better discrimination than BMI of hypertension and elevated glucose, and of raised TC for men. Information on four new anthropometric indices did not improve model fit or subject discrimination. CONCLUSION: For BP/hypertension, glucose/elevated glucose, and TC/raised TC, WC was more informative than BMI for Vietnamese men, but both WC and BMI were important for Vietnamese women. Both WC and BMI need to be assessed for estimation of CVD risk in Vietnam.

National survey of risk factors for non-communicable disease in Vietnam: prevalence estimates and an assessment of their validity.

BACKGROUND: To estimate the prevalence of non-communicable disease (NCD) risk factors at a provincial level in Vietnam, and to assess whether the summary estimates allow reliable inferences to be drawn regarding regional differences in risk factors and associations between them. METHODS: Participants (n = 14706, 53.5 % females) aged 25-64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Data were analysed using complex survey methods. RESULTS: Differences by sex in mean years of schooling (males 8.26 ± 0.20, females 7.00 ± 0.18), proportions of current smokers (males 57.70 %, females 1.73 %), and binge-drinkers (males 25.11 %, females 0.63 %), and regional differences in diet, reflected the geographical and socio-cultural characteristics of the country. Provinces with a higher proportion of urban population had greater mean levels of BMI (r = 0.82), and lesser proportions of active people (r = -0.89). The associations between the summary estimates were generally plausible (e.g. physical activity and BMI, r = -0.80) but overstated, and with some anomalous findings due to characterisation of smoking and hypertension by STEPS protocols. CONCLUSIONS: This report provides an extensive description of the sex-specific and regional distribution of NCD risk factors in Vietnam and an account of some health-related consequences of industrialisation in its early stages. The STEPS protocols can be utilized to provide aggregate data for valid between-population comparisons, but with important caveats identified.

Fruit and vegetable consumption in Vietnam, and the use of a 'standard serving' size to measure intake.

The aims of the present study were to provide nationally representative data on fruit and vegetable consumption in Vietnam, and to assess the accuracy of the reported numbers of 'standard servings' consumed. Data analysed were from a multi-stage stratified cluster survey of 14 706 participants (46·5 % males, response proportion 64·1 %) aged 25-64 years in Vietnam. Measurements were made in accordance with the WHO STEPwise approach to surveillance of non-communicable diseases (STEPS) protocols. Approximately 80 % of Vietnamese people reported having less than five servings of fruit and vegetables daily in a typical week. Fruit and vegetable intake reported in 'standard serving' sizes was positively correlated with levels of education completed and household income (P<0·001 for trend). The correlations between summary values for each province reflect some known demographic, geographical and climatic characteristics of the country. For example, provinces at higher latitude had higher mean servings of vegetables (r 0·90), and provinces with higher proportions of urban population had higher mean servings of fruit (r 0·40). In conclusion, about eight in ten Vietnamese people aged 25-64 years did not meet WHO recommendations for daily consumption of at least five servings of fruit and vegetables. On the basis of the consistency of the data collected with other estimates and with physical and demographic characteristics of the country, the WHO STEPS instrument has construct validity for measuring fruit and vegetable intake, but with two issues identified. The issues were seasonal variation in reporting and a limitation on the usefulness of the information for associative analyses.

Alcohol Consumption in Vietnam, and the Use of 'Standard Drinks' to Measure Alcohol Intake.

AIMS: To provide nationally representative data on alcohol consumption in Vietnam and to assess whether reported numbers of 'standard drinks' consumed have evidence of validity (particularly in rural areas where home-made alcohol is consumed from cups of varying size). METHODS: A nationally representative population-based survey of 14,706 participants (46.5% males, response proportion 64.1%) aged 25-64 years in Vietnam. Measurements were made in accordance with WHO STEPS protocols. Data were analysed using complex survey methods. RESULTS: Among men, 80% reported drinking alcohol during the last year, and 40% were hazardous/harmful drinkers. Approximately 60% of men and <5% of women had consumed alcohol during the last week, with one-in-four of the men reporting having consumed at least five standard drinks on at least one occasion. Numbers of standard drinks reported by men were associated with blood pressure/hypertension, particularly in rural areas (P < 0.001 for trend). Most of the calibration and discrimination possible from self-reported information on alcohol consumption was provided by binary responses to questions on whether or not alcohol had been consumed during the reference period. CONCLUSION: Alcohol use and harmful consumption were common among Vietnamese men but less pronounced than in Western nations. Self-reports of quantity of alcohol consumed in terms of standard drinks had predictive validity for blood pressure and hypertension even in rural areas. However, using detailed measures of consumption resulted in only minor improvements in prediction compared to simple measures.

Physical Activity in Vietnam: Estimates and Measurement Issues.

INTRODUCTION: Our aims were to provide the first national estimates of physical activity (PA) for Vietnam, and to investigate issues affecting their accuracy. METHODS: Measurements were made using the Global Physical Activity Questionnaire (GPAQ) on a nationally-representative sample of 14706 participants (46.5% males, response 64.1%) aged 25-64 years selected by multi-stage stratified cluster sampling. RESULTS: Approximately 20% of Vietnamese people had no measureable PA during a typical week, but 72.9% (men) and 69.1% (women) met WHO recommendations for PA by adults for their age. On average, 52.0 (men) and 28.0 (women) Metabolic Equivalent Task (MET)-hours/week (largely from work activities) were reported. Work and total PA were higher in rural areas and varied by season. Less than 2% of respondents provided incomplete information, but an additional one-in-six provided unrealistically high values of PA. Those responsible for reporting errors included persons from rural areas and all those with unstable work patterns. Box-Cox transformation (with an appropriate constant added) was the most successful method of reducing the influence of large values, but energy-scaled values were most strongly associated with pathophysiological outcomes. CONCLUSIONS: Around seven-in-ten Vietnamese people aged 25-64 years met WHO recommendations for total PA, which was mainly from work activities and higher in rural areas. Nearly all respondents were able to report their activity using the GPAQ, but with some exaggerated values and seasonal variation in reporting. Data transformation provided plausible summary values, but energy-scaling fared best in association analyses.

Clinical Characteristics Are Similar across Type A and B Influenza Virus Infections.

BACKGROUND: Studies that aimed at comparing the clinical presentation of influenza patients across virus types and subtypes/lineages found divergent results, but this was never investigated using data collected over several years in a countrywide, primary care practitioners-based influenza surveillance system. METHODS: The IBVD (Influenza B in Vircases Database) study collected information on signs and symptoms at disease onset from laboratory-confirmed influenza patients of any age who consulted a sentinel practitioner in France. We compared the clinical presentation of influenza patients across age groups (0-4, 5-14, 15-64 and 65+ years), virus types (A, B) and subtypes/lineages (A(H3N2), pandemic A(H1N1), B Victoria, B Yamagata). RESULTS: Overall, 14,423 influenza cases (23.9% of which were influenza B) were included between 2003-2004 and 2012-2013. Influenza A and B accounted for over 50% of total influenza cases during eight and two seasons, respectively. There were minor differences in the distribution of signs and symptoms across influenza virus types and subtypes/lineages. Compared to patients aged 0-4 years, those aged 5-14 years were more likely to have been infected with type B viruses (OR 2.15, 95% CI 1.87-2.47) while those aged 15-64 years were less likely (OR 0.83, 95% CI 0.73-0.96). Males and influenza patients diagnosed during the epidemic period were less likely to be infected with type B viruses. CONCLUSIONS: Despite differences in age distribution, the clinical illness produced by the different influenza virus types and subtypes is indistinguishable among patients that consult a general practitioner for acute respiratory infections.

Ten influenza seasons in France: distribution and timing of influenza A and B circulation, 2003-2013.

BACKGROUND: Describing the circulation of influenza viruses and the characteristics of seasonal epidemics remains an essential tool to optimize the strategies of influenza prevention and control. Special attention has been recently paid to influenza B in the context of the availability of a quadrivalent vaccine, containing two influenza B strains. METHODS: We used data from a practitioners-based influenza surveillance network to describe the circulation of influenza viruses in France from 2003-2004 to 2012-2013. Nasopharyngeal swabs taken from acute respiratory infection (ARI) patients between October and April were tested for influenza. We reported the number of influenza cases by virus type (A, B), subtype (A(H1), A(H3)) and B lineage (Yamagata, Victoria) in each season and determined the frequency of influenza B vaccine mismatch. We estimated weekly incidence of influenza by extrapolating reported influenza cases to the French population. We compared the temporal characteristics of the epidemics caused by influenza A(H1), A(H3) and B. RESULTS: Overall, 49,919 ARI patients were tested, of which 16,287 (32.6 %) were positive for influenza. Type B virus caused 23.7 % of all influenza cases. Virus subtypes A(H1) and A(H3) caused 51.6 % and 48.4 % of influenza A cases, respectively. Viruses of the B-Yamagata and B-Victoria lineage caused 62.8 % and 37.2 % of influenza B cases, respectively. There was an influenza B vaccine mismatch in three of the five seasons where influenza B caused 10 % or more of all influenza cases. Influenza A(H3) had the highest average value of estimated weekly incidence during the study period. Influenza B peaked an average 3.8 weeks later than influenza A when both virus types were circulating. No differences in the duration of influenza A and B epidemics were observed. CONCLUSIONS: Influenza A(H3) was the most prevalent influenza type during the study period. Influenza B caused around one fourth of all influenza cases and tended to circulate later than influenza A. The frequency of influenza B vaccine mismatches was substantial. Timely data on the circulation of influenza viruses collected within influenza surveillance systems are essential to optimize influenza prevention and control strategies.

Declining Prevalence of Tobacco Smoking in Vietnam.

INTRODUCTION: To supplement limited information on tobacco use in Vietnam, data from a nationally-representative population-based survey was used to estimate the prevalence of smoking among 25-64 year-olds. METHODS: This study included 14,706 participants (53.5% females, response proportion 64%) selected by multi-stage stratified cluster sampling. Information was collected using the World Health Organization STEPwise approach to surveillance of risk factors for non-communicable disease (STEPS) questionnaire. Smoking prevalence was estimated with stratification by age, calendar year, and birth year. RESULTS: Prevalence of ever-smoking was 74.9% (men) and 2.6% (women). Male ever-smokers commenced smoking at median age of 19.0 (interquartile range [IQR]: 17.0, 21.0) years and smoked median quantities of 10.0 (IQR: 7.0, 20.0) cigarettes/day. Female ever-smokers commenced smoking at median age of 20.0 (IQR: 18.0, 26.0) years and smoked median quantities of 6.0 (IQR: 4.0, 10.0) cigarettes/day. Prevalence has decreased in recent cohorts of men (p = .001), and its inverse association with years of education (p < .001) has strengthened for those born after 1969 (interaction p < .001). At 60 years of age, 53.0% of men who had reached that age were current smokers and they had accumulated median exposures of 39.0 (IQR: 32.0, 42.0) years of smoking and 21.0 (IQR: 11.5, 36.0) pack-years of cigarettes. The proportion of ever-smokers has decreased consistently among successive cohorts of women (p < .001). CONCLUSIONS: Smoking prevalence is declining in recent cohorts of men, and continues to decline in successive cohorts of women, possibly in response to anti-tobacco initiatives commencing in the 1990s. Low proportions of quitters mean that Vietnamese smokers accumulate high exposures despite moderate quantities of cigarettes smoked per day.