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Methanogens are important hydrogen consumers in the gut and are associated with differing host health. Here, we determine the prevalence and abundance of archaeal species in the guts of a multi-ethnic cohort of healthy Singapore residents.

Methanogenic Archaea (methanogens) are a phylogenetically diverse group of microorganisms and are considered to be the most abundant archaeal representatives in the human gut. However, the gut methanogen diversity of human populations in many global regions remains poorly investigated. Here, we report the abundance and diversity of gut methanogenic Archaea in a multi-ethnic cohort of healthy Singaporeans by using a concerted approach of metagenomic sequencing, 16S rRNA gene amplicon sequencing, and quantitative PCR. Our results indicate a mutual exclusion of

Background: Both high energy density and fast eating rates contribute to excess energy intakes. The energy intake rate (EIR; kcal/min) combines both the energy density (kcal/g) and eating rate (g/min) of a food to quantify the typical rate at which calories of different foods are ingested. Objectives: We describe the EIRs of diets in a multi-ethnic Asian population, and examine relationships between the consumption of high-EIR foods and total energy intake, body composition, and cardio-metabolic risk factors. Methods: Diet and lifestyle data from the Singapore Multi-Ethnic Cohort 2 (n = 7011; 21-75 y), were collected through interviewer-administrated questionnaires. The EIR for each of the 269 foods was calculated as the product of its eating rate and energy density. Multivariable models were used to examine associations between the relative consumption of foods with higher and lower EIRs and energy intake, body composition, and cardio-metabolic risks, after adjusting for age, sex, ethnicity, education level, physical activity, smoking status, and alcohol drinking status. Results: Individuals with higher daily energy intakes and with obesity consumed a significantly larger percentage of their energy from high-EIR foods, with a smaller relative intake of lower-EIR foods. Individuals with raised serum cholesterol also consumed a significantly higher proportion of high-EIR foods, whereas those without hypertension consumed a larger percentage of energy intake from low-EIR foods. Individuals classified as having a "very high"dietary EIR had a significantly 1.3 kg higher body weight (95% CI, 0.2-1.5; P = 0.013), 0.4 kg/m2 higher BMI (95% CI, 0.03-0.8; P = 0.037), and 1.2 cm larger waist circumference (95% CI, 0.2-2.2; P = 0.010), and were more likely to have abdominal overweight (OR, 1.3; 95% CI, 1.1-1.5; P < 0.001) than those with a "low"dietary EIR. Conclusions: Comparing foods by their EIRs summarizes the combined impact of energy density and eating rate, and may identify foods and dietary patterns that are associated with obesogenic eating styles and higher diet-related cardiovascular disease risk in an Asian population.

Objectives The recently discovered tigecycline-inactivating enzyme Tet(X4) can confer high-level tigecycline resistance on its hosts, which makes it a public health concern. This study focused on isolation and screening of Tet(X4)-positive Enterobacteriaceae from the gut microbiota of a cohort of healthy individuals in Singapore. Methods MinION and Illumina sequencing was performed to obtain the complete genome sequences of Escherichia coli 2EC1-1 and 94EC. Subsequently, 109 human faecal samples were screened retrospectively for eravacycline-resistant Enterobacteriaceae strains, which were further tested for tet(X4) by PCR. The taxonomy of the isolated strains was determined by 16S rRNA gene PCR and Sanger sequencing. Results Comparative genomic analysis of E. coli 2EC1-1 and 94EC revealed that both carry tet(X4), which is encoded by IncI1-type plasmids p2EC1-1 and p94EC-2, respectively. Retrospective screening of faecal samples collected from 109 healthy individuals showed that the faecal carriage rate of Tet(X4)-producing Enterobacteriaceae is 10.1% (95% CI = 5.1%–17.3%), suggesting that tet(X4) is widely distributed in the gut microbiota of healthy individuals in Singapore. Conclusions To the best of our knowledge, this is the first report on the prevalence of tet(X4) in the gut microbiota of a healthy human cohort, as well as the first description of this resistance mechanism outside of China. Our findings suggest that surveillance of tet(X4) in community settings is vital to monitor the spread of this resistance mechanism.

Multidrug-resistant (MDR) Escherichia coli strains that carry extended-spectrum β-lactamases (ESBLs) or colistin resistance gene mcr-1 have been identified in the human gut at an increasing incidence worldwide. In this study, we isolated and characterized MDR Enterobacteriaceae from the gut microbiota of healthy Singaporeans and show that the detection rates for ESBL-producing and mcr-positive Enterobacteriaceae are 25.7% (28/109) and 7.3% (8/109), respectively. Whole-genome sequencing analysis of the 37 E. coli isolates assigned them into 25 sequence types and 6 different phylogroups, suggesting that the MDR E. coli gut colonizers are highly diverse. We then analyzed the genetic context of the resistance genes and found that composite transposons played important roles in the cotransfer of blaCTX-M-15/55 and qnrS1, as well as the acquisition of mcr-1. Furthermore, comparative genomic analysis showed that 12 of the 37 MDR E. coli isolates showed high similarity to ESBL-producing E. coli isolates from raw meat products in local markets. By analyzing the core genome single nucleotide polymorphisms (SNPs) shared by these isolates, we identified possible clonal transmission of an MDR E. coli clone between human and raw meat, as well as a group of highly similar IncI2 (Delta) plasmids that might be responsible for the dissemination of mcr-1 in a much wider geographic region. Together, these results suggest that antibiotic resistance may be transmitted between different environmental settings by the expansion of MDR E. coli clones, as well as by the dissemination of resistance plasmids. IMPORTANCE The human gut can harbor both antibiotic-resistant and virulent Escherichia coli which may subsequently cause infections. In this study, we found that multidrug-resistant (MDR) E. coli isolates from the gut of healthy Singaporeans carry a diverse range of antibiotic resistance mechanisms and virulence factor genes and are highly diverse. By comparing their genomes with the extended-spectrum β-lactamase (ESBL)-producing E. coli isolates from raw meat products that were sampled at a similar time from local markets, we detected an MDR E. coli clone that was possibly transmitted between humans and raw meat products. Furthermore, we also found that a group of resistance plasmids might be responsible for the dissemination of colistin resistance gene mcr-1 in Singapore, Malaysia, and Europe. Our findings call for better countermeasures to block the transmission of antibiotic resistance.

Importance: Since January 2020, Singapore has implemented comprehensive measures to suppress SARS-CoV-2. Despite this, the country has experienced contrasting epidemics, with limited transmission in the community and explosive outbreaks in migrant worker dormitories. Objective: To estimate SARS-CoV-2 infection incidence among migrant workers and the general population in Singapore. Design: Prospective serological cohort studies. Setting: Two cohort studies — in a migrant worker dormitory and in the general population in Singapore. Participants: 478 residents of a SARS-CoV-2-affected migrant worker dormitory were followed up between May and July 2020, with blood samples collected on recruitment and after 2 and 6 weeks. In addition, 937 community-dwelling adult Singapore residents, for whom pre-pandemic sera were available, were recruited. These individuals also provided a serum sample on recruitment in November/December 2020. Exposure: Exposure to SARS-CoV-2 in a densely populated migrant worker dormitory and in the general population. Main outcomes and measures: The main outcome measures were the incidences of SARS-CoV-2 infection in migrant workers and in the general population, as determined by the detection of neutralizing antibodies against SARS-CoV-2, and adjusting for assay sensitivity and specificity using a Bayesian modeling framework. Results: No evidence of community SARS-CoV-2 exposure was found in Singapore prior to September 2019. It was estimated that < 2 per 1000 adult residents in the community were infected with SARS-CoV-2 in 2020 (cumulative seroprevalence: 0.16%; 95% CrI: 0.008–0.72%). Comparison with comprehensive national case notification data suggested that around 1 in 4 infections in the general population were associated with symptoms. In contrast, in the migrant worker cohort, almost two-thirds had been infected by July 2020 (cumulative seroprevalence: 63.8%; 95% CrI: 57.9–70.3%); no symptoms were reported in almost all of these infections. Conclusions and relevance: Our findings demonstrate that SARS-CoV-2 suppression is possible with strict and rapid implementation of border restrictions, case isolation, contact tracing, quarantining, and social-distancing measures. However, the risk of large-scale epidemics in densely populated environments requires specific consideration in preparedness planning. Prioritization of these settings in vaccination strategies should minimize the risk of future resurgences and potential spillover of transmission to the wider community.

Multidrug resistant (MDR) Escherichia coli strains that carry extended-spectrum β-lactamases (ESBLs) or colistin resistance gene mcr-1 have been identified in the human gut at an increasing incidence worldwide. In this study, we sampled and characterized MDR Enterobacteriaceae from the gut microbiota of healthy Singaporeans and show that the prevalence of ESBL-producing and mcr-positive Enterobacteriaceae is 26.6% and 7.3%, respectively. Whole-genome sequencing of 37 E. coli isolates identified 25 sequence types and assigned them into six different phylogroups, suggesting that the human intestinal MDR E. coli strains are highly diverse. In addition, we found that E. coli isolates belonging to phylogroup D, B2 and F carry a higher number of virulence genes, whereas isolates of phylogroup A, B1 and E carry fewer virulence factor genes but are frequent carriers of florfenicol resistance gene floR and colistin resistance gene mcr-1. Comparison of the seven mcr-1-positive E. coli isolates revealed that mcr-1 is carried by conjugative plasmids or embedded in composite transposons, which could potentially mobilize mcr-1 to other pathogenic Enterobacteriaceae strains or MDR plasmids. Finally, we found that 12 out of the 37 MDR E. coli isolates in this study show high similarity to ESBL-producing E. coli isolates from raw meats from local markets, suggesting a potential transmission of MDR E. coli from meat products to the human gut microbiota. Our findings show diverse antibiotic resistance and virulence profiles of intestinal E. coli and call for better countermeasures to block the transmission of MDR E. coli via the food chain.ImportanceThe human gut can harbor both antibiotic resistant and virulent E. coli which may subsequently cause infections. In this study, the antibiotic resistance and virulence traits of antibiotic-resistant E. coli isolates from human gut microbiota of healthy subjects were investigated. The isolated E. coli strains carry a diverse range of antibiotic resistance mechanisms and virulence factor genes, are highly diverse to each other, and are likely to originate from raw meat products from the local markets. Of particular concern are seven E. coli isolates which carry colistin resistance gene mcr-1. This gene can be mobilized into other pathogens and MDR plasmids, thereby spreading resistance to the last-resort antibiotic colistin. Our findings also suggest that raw meat could serve as important source to transmit MDR bacteria into the human gut microbiota.

By using a rapid whole-blood T cell activation assay measuring cytokines released by SARS-CoV-2–specific T cells, Le Bert et al. show that individuals who clear SARS-CoV-2 infection without symptoms mount a highly functional virus-specific cellular immune response., The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between antiviral and inflammatory features. SARS-CoV-2–specific T cells in individuals who clear SARS-CoV-2 without symptoms could reveal nonpathological yet protective characteristics. We longitudinally studied SARS-CoV-2–specific T cells in a cohort of asymptomatic (n = 85) and symptomatic (n = 75) COVID-19 patients after seroconversion. We quantified T cells reactive to structural proteins (M, NP, and Spike) using ELISpot and cytokine secretion in whole blood. Frequencies of SARS-CoV-2–specific T cells were similar between asymptomatic and symptomatic individuals, but the former showed an increased IFN-γ and IL-2 production. This was associated with a proportional secretion of IL-10 and proinflammatory cytokines (IL-6, TNF-α, and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2–specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2–infected individuals are not characterized by weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response., Graphical Abstract

The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion (IL-2, IFN-γ, IL-4, IL-6, IL-1β, TNF-α and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-γ and IL-2 production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 and pro-inflammatory cytokines (IL-6, TNF-α and IL-1β) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 might help to reduce inflammatory events during viral clearance.

Eating faster is associated with greater body mass index (BMI), but less is known about the relationships between eating rate, energy intake, body composition, and cardio-metabolic risk factors in different Asian ethnic groups. Using data from the Singapore Multi-Ethnic Cohort (n = 7011, 21&ndash, 75 y), we investigated associations between self-reported eating rate (SRER), with energy intake, body composition, blood pressure, and blood lipids. SRER and lifestyle was assessed using interviewer-administered questionnaires. Multivariable models were used to examine the associations of SRER with energy intake, body composition, blood pressure, and blood lipids after adjusting for covariates. General and abdominal overweight were defined as BMI &ge, 23 kg/m2 and waist circumference &gt, 90cm (men) and &gt, 80cm (women), respectively. On average, faster eaters (vs. slower eaters) consumed 105kcal/day more (p = 0.034), had ~5kg higher body weight (p &lt, 0.001), 1.3 kg/m2 higher BMI (p &lt, 0.001), and 3.1cm larger waist-circumference (p &lt, 0.001). Faster eaters had significantly higher blood pressure, circulating triglycerides, and total-to-high-density lipoprotein cholesterol ratio than slower eaters. Faster eaters were twice as likely to develop general (multivariable-OR: 2.2, 95%CI,1.8&ndash, 2.6, p &lt, 0.001), and abdominal (OR:1.8, 95%CI, 1.5&ndash, 2.2, 0.001) overweight than slower eaters. This association was observed across all subgroups by age, sex, and ethnicity. Findings suggest that SRER is a robust behavioral marker for increased risk of higher energy intake, obesity, and poor cardio-metabolic health, and a modifiable behavioral risk-factor for obesity prevention.

Objectives: This first cross-sectional survey on latent tuberculosis infection (LTBI) in Singapore was performed by utilizing the QuantiFERON Gold In-tube (QFT-GIT) assay to collect data on the prevalence of LTBI and to identify potential risk factors associated with LTBI. Methods: Nationwide household addresses were selected randomly for enumeration, and Singaporeans or Permanent Residents aged 18–79 years were identified. One eligible member per household was selected using the Kish grid. Each participant answered a questionnaire assessing their medical history (including tuberculosis (TB)), socio-economic factors, and lifestyle factors. They also provided a blood specimen for the QFT-GIT assay. Participants with a positive QFT-GIT result were defined as having LTBI if they were asymptomatic. To identify independent risk factors, adjusted hazard ratios were obtained using the multivariable modified Breslow–Cox proportional hazards model. Results: An overall QFT-GIT positivity rate of 12.7% was detected amongst 1682 Singapore residents. There was a wide variation in the positivity rate according to the participants’ country of birth. Higher LTBI prevalence was also significantly associated with increasing age, lower educational and socio-economic status, and alcohol use. Conclusions: Given the high prevalence of LTBI amongst foreign-born residents from regional countries, similar studies should be conducted amongst migrants in Singapore to improve national guidelines on screening and preventive treatment against LTBI. Keywords: Latent tuberculosis, Interferon-gamma release assay, Prevalence, Risk factors, Population

Summary Background Healthcare workers (HCWs) may be the inadvertent interface between the healthcare setting and the community for infectious diseases transmission. Aim To investigate HCWs' contacts during a work day and compare these against working adults from the general population. Methods Prospective survey of contacts through 24 h self-reported diary in three public sector tertiary care hospitals and community-based working adults in Singapore. Participants were HCWs and working adults from the community. Findings In all, 211 HCWs and 1028 working adults reported a total of 4066 and 9206 contacts. HCWs reported more work-related contacts than community-based working adults (median of 13 versus 4), and more contacts that were neither household nor work-related (1 versus 0) but fewer household contacts (2 versus 3). HCWs reported more work-related contacts involving physical contacts, and more new contacts particularly with short duration (≤15 min) compared to community-based working adults. Among different HCW types, doctors reported the highest whereas ward-based nurses reported the lowest total work-related contacts. Around half of ward-based and clinic-based nurses' contacts involved physical touch. Work-related contacts reported by clinic-based nurses, doctors, and assorted HCWs were shorter than in ward-based nurses, with a substantial number effectively occurring with new contacts. Institutional effects significant on univariate analyses were much reduced and non-significant after adjusting for confounding by HCW type. Conclusion HCWs' contacts differ substantially from those of community-based working adults. HCWs may thus be at higher risk of acquiring and spreading contact-transmissible and respiratory infections due to the nature of their work. Whereas total number of contacts was fairly similar between HCW types, the characteristics of their contacts differed substantively.

We assessed and found cross-protection between the influenza pandemic and 2 seasonal viruses that circulated in Singapore. Age-related differences in disease severity between the subtypes were investigated, and we demonstrate birth cohort effects consistent with the theory of antigenic sin., Background After 2009, pandemic influenza A(H1N1) [A(H1N1)pdm09] cocirculated with A(H3N2) and B in Singapore. Methods A cohort of 760 participants contributed demographic data and up to 4 blood samples each from October 2009 to September 2010. We compared epidemiology of the 3 subtypes and investigated evidence for heterotypic immunity through multivariable logistic regression using a generalized estimating equation. To examine age-related differences in severity between subtypes, we used LOESS (locally weighted smoothing) plots of hospitalization to infection ratios and explored birth cohort effects referencing the pandemic years (1957; 1968). Results Having more household members aged 5–19 years and frequent public transport use increased risk of infection, while preexisting antibodies against the same subtype (odds ratio [OR], 0.61; P = .002) and previous influenza infection against heterotypic infections (OR, 0.32; P = .045) were protective. A(H1N1)pdm09 severity peaked in those born around 1957, while A(H3N2) severity was least in the youngest individuals and increased until it surpassed A(H1N1)pdm09 in those born in 1952 or earlier. Further analysis showed that severity of A(H1N1)pdm09 was less than that for A(H3N2) in those born in 1956 or earlier (P = .021) and vice versa for those born in 1968 or later (P < .001), with no difference in those born between 1957 and 1967 (P = .632). Conclusions Our findings suggest that childhood exposures had long-term impact on immune responses consistent with the theory of antigenic sin. This, plus observations on short-term cross-protection, have implications for vaccination and influenza epidemic and pandemic mitigation strategies.

The Singapore Integrative Omics Study provides valuable insights on establishing population reference measurement in 364 Chinese, Malay, and Indian individuals. These measurements include > 2.5 millions genetic variants, 21,649 transcripts expression, 282 lipid species quantification, and 284 clinical, lifestyle, and dietary variables. This concept paper introduces the depth of the data resource, and investigates the extent of ethnic variation at these omics and non-omics biomarkers. It is evident that there are specific biomarkers in each of these platforms to differentiate between the ethnicities, and intra-population analyses suggest that Chinese and Indians are the most biologically homogeneous and heterogeneous, respectively, of the three groups. Consistent patterns of correlations between lipid species also suggest the possibility of lipid tagging to simplify future lipidomics assays. The Singapore Integrative Omics Study is expected to allow the characterization of intra-omic and inter-omic correlations within and across all three ethnic groups through a systems biology approach., The Singapore Genome Variation projects characterized the genetics of Singapore’s Chinese, Malay, and Indian populations. The Singapore Integrative Omics Study introduced here goes further in providing multi-omic measurements in individuals from these populations, including genetic, transcriptome, lipidome, and lifestyle data, and will facilitate the study of common diseases in Asian communities.

Background: The multidimensional Positive Mental Health Instrument (PMHI) has 47 items and six subscales. This study aimed to develop and validate a short unidimensional version of the PMHI among Singapore’s adult resident population. Methods: Using pooled data from three earlier studies (n = 1050), PMHI items were reduced by Partial Credit Rasch Model (PCRM) runs in a random split-half sample, while psychometric properties of the resulting measure were tested through confirmatory factor analysis (CFA), item response theory-graded response model and internal consistency reliability in the other half. Its reliability, construct and concurrent validity, agreement with the original scale, floor and ceiling effect, and scale estimates were further investigated in an external representative general population sample (n = 1925). Results: The average age of the participants was around 41 years. Four PCRM re-runs for item selection resulted in a 6-item unidimensional Rapid PMHI (R-PMHI). CFA confirmed the unidimensional structure of the R-PMHI in the internal (RMSEA = 0.075, CFI = 0.985, TLI = 0.974) and external (RMSEA = 0.051, CFI = 0.992, TLI = 0.987) validation samples. In the external validation sample, the R-PMHI met concurrent validity criteria, showing high agreement with the 47-item version with intra-class correlation coefficient of 0.872 (95% CI: 0.861 to 0.882) and low floor and ceiling effects. Weight-adjusted mean (SE, 95% CI) R-PMHI score in the population was 4.86 (0.2, 4.82–4.90). Conclusion: The unidimensional 6-item R-PMHI offers brevity over the original multidimensional measure while appropriately representing the positive mental health construct. Prospective studies are needed to assess its responsiveness and test-retest reliability. Ministry of Health (MOH) National Medical Research Council (NMRC) Published version Study 1 was supported by funding from the Ministry of Health, Singapore and the Singapore Millennium Foundation of the Temasek Trust (Grant number RF08–01). Studies 2 and 3 were funded by the Singapore Ministry of Health’s National Medical Research Council under the Centre Grant Programme (Grant number NMRC/CG12Aug04). Study 4 was supported by grants from the Ministry of Health, Singapore, National University of Singapore and National University Health System, Singapore (Grant number NA). The study funders played no role in this study design or data analysis.

Background: We assessed the associations of sleep, physical activity and sedentary behaviour with positive mental health (PMH) in the multi-ethnic population of Singapore. Methods: The Singapore Health 2 study is a nationally representative cross-sectional survey among residents aged 18&ndash, 79 years. A PMH instrument was administered to 1925 participants to obtain total PMH and six sub-component scores. Self-rated sleep duration, sleep quality, sedentary behaviour and physical activity were assessed. Multivariable linear regression analyses were conducted. Results: The mean age of the participants was 40.1 (SD 14.3) years. Sleep duration (&ge, 8 h/night: &beta, = 0.17,95% CI: 0.02&ndash, 0.32, 7- &lt, = 0.17,95% CI: 0.03&ndash, 0.30 versus &lt, 6 h/night, p = 0.002), sleep quality (very good: &beta, = 0.45,95% CI: 0.29&ndash, 0.60, fairly good: &beta, = 0.20,95% CI: 0.06&ndash, 0.33 versus very/fairly bad, ptrend &lt, 0.001) and physical activity (high: &beta, = 0.19,95% CI: 0.05&ndash, moderate: &beta, = 0.15, 95% CI: 0.03&ndash, 0.27 versus low, 0.001) were directly associated with total PMH. Sedentary behaviour was not significantly associated with PMH. Sleep duration, sleep quality and physical activity were directly associated with the PMH sub-components &lsquo, emotional support&rsquo, and &lsquo, personal growth and autonomy&rsquo, Conclusions: Duration and quality of sleep and physical activity were directly associated with PMH in an urban Asian population. These findings support incorporating sleep and physical activity interventions to improve population mental health.

PurposeThe diabetic cohort (DC) was set up to study the determinants of complications in individuals with type 2 diabetes and examine the role of genetic, physiological and lifestyle factors in the development of complications in these individuals.ParticipantsA total of 14 033 adult participants with type 2 diabetes were recruited from multiple public sector polyclinics and hospital outpatient clinics in Singapore between November 2004 and November 2010. The first round of follow-up was conducted for 4131 participants between 2012 and 2016; the second round of follow-up started in 2016 and is expected to end in 2021. A questionnaire survey, physical assessments, blood and urine sample collection were conducted at recruitment and each follow-up visit. The data set also includes genetic data and linkage to medical and administrative records for recruited participants.Findings to dateData from the cohort have been used to identify determinants of diabetes and related complications. The longitudinal data of medical records have been used to analyse diabetes control over time and its related outcomes. The cohort has also contributed to the identification of genetic loci associated with type 2 diabetes and diabetic kidney disease in collaboration with other large cohort studies. About 25 scientific papers based on the DC data have been published up to May 2019.Future plansThe rich data in DC can be used for various types of research to study disease-related complications in patients with type 2 diabetes. We plan to further investigate disease progression and new biomarkers for common diabetic complications, including diabetic kidney disease and diabetic neuropathy.

Low levels of 25-hydroxyvitamin D (25(OH)D) has been associated with many negative health outcomes including falls and fractures. 25(OH)D is largely bound to vitamin D binding protein (VDBP). There is increasing evidence that free or bioavailable 25(OH)D may be a better measure of vitamin D deficiency. To determine the prevalence of 25(OH)D deficiency and VDBP levels in multi-ethnic population, and its impact on muscle strength. Cross-sectional study of older adults in Western region of Singapore. 295 participants from three ethnic groups were selected from the Healthy Older People Everyday (HOPE) cohort for measurements of total 25(OH)D and VDBP levels. Total 25(OH)D, VDBP, frailty status, Timed-Up-and-Go (TUG) and grip strength (GS) were assessed. Albumin, free and bioavailable 25(OH)D were only available for 256 participants. 53% of Malay and 55% of Indians were deficient in 25(OH)D compared with 18.2% of ethnic Chinese participants. Chinese also had higher total 25(OH)D concentrations with a mean of 29.1 ug/l, (p =

Background Measures of mental well-being and positive mental health (PMH) have been largely developed and used in Western populations, however, data on representative Asian communities are lacking. Using data from a population sample, this study sought to establish psychometric properties and norms of the PMH Instrument (PMH-I), a measure of positive mental health developed in Singapore. Methods We conducted a nationally representative survey among 1925 adults aged 18–79 years of Chinese, Malay, Indian or other ethnicity. Participants reported socio-demographic characteristics and completed the PMH-I along with measures of health-related quality of life (HRQoL) and psychological distress. Construct validity of the PMH-I was assessed using confirmatory factor analysis and concurrent validity was tested through correlation with other psychological measures. Normative PMH values and differences in population subgroups were estimated. Results The six-factor-higher-order structure of the PMH-I comprising six subscales of general coping, emotional support, spirituality, interpersonal skills, personal growth and autonomy and global affect was confirmed. Concurrent validity was shown through significant positive correlation of the total PMH score and its subscales with HRQoL and an inverse correlation with psychological distress. Weighted age, gender and ethnicity-specific norms were derived for the Singapore population. Total PMH was significantly higher in participants aged over 40 years as compared with 18–29 year olds and in non-Chinese ethnic groups as compared with Chinese. These differences were observed for all PMH-I subscales, with the exception of emotional support and interpersonal skills score differences by age. In contrast, gender, marital status, and education level were significantly associated with some of the subscales, but not with total PMH. Conclusions These results support the psychometric properties of the PMH-I in a multi-ethnic Asian population sample. The generalizable population-based norms support the application of the PMH-I for measuring mental health and assessing its determinants within the Singapore general population. Electronic supplementary material The online version of this article (10.1186/s12874-018-0487-9) contains supplementary material, which is available to authorized users.

Background Singapore remains vulnerable to worldwide epidemics due to high air traffic with other countries This study aims to measure the public’s awareness of the Middle East Respiratory Syndrome (MERS) and Avian Influenza A (H7N9), identify population groups who are uninformed or misinformed about the diseases, understand their choice of outbreak information source, and assess the effectiveness of communication channels in Singapore. Methods A cross-sectional study, comprising of face-to-face interviews, was conducted between June and December 2013 to assess the public’s awareness and knowledge of MERS and H7N9, including their choice of information source. Respondents were randomly selected and recruited from 3 existing cohort studies. An opportunistic sampling approach was also used to recruit new participants or members in the same household through referrals from existing participants. Results Out of 2969 participants, 53.2% and 79.4% were not aware of H7N9 and MERS respectively. Participants who were older and better educated were most likely to hear about the diseases. The mean total knowledge score was 9.2 (S.D ± 2.3) out of 20, and 5.9 (S.D ± 1.2) out of 10 for H7N9 and MERS respectively. Participants who were Chinese, more educated and older had better knowledge of the diseases. Television and radio were the primary sources of outbreak information regardless of socio-demographic factors. Conclusion Heightening education of infectious outbreaks through appropriate media to the young and less educated could increase awareness.

The major histocompatibility complex (MHC) containing the classical human leukocyte antigen (HLA) Class I and Class II genes is among the most polymorphic and diverse regions in the human genome. Despite the clinical importance of identifying the HLA types, very few databases jointly characterize densely genotyped single nucleotide polymorphisms (SNPs) and HLA alleles in the same samples. To date, the HapMap presents the only public resource that provides a SNP reference panel for predicting HLA alleles, constructed with four collections of individuals of north-western European, northern Han Chinese, cosmopolitan Japanese and Yoruba Nigerian ancestry. Owing to complex patterns of linkage disequilibrium in this region, it is unclear whether the HapMap reference panels can be appropriately utilized for other populations. Here, we describe a public resource for the Singapore Genome Variation Project with: (i) dense genotyping across ∼ 9000 SNPs in the MHC; (ii) four-digit HLA typing for eight Class I and Class II loci, in 96 southern Han Chinese, 89 Southeast Asian Malays and 83 Tamil Indians. This resource provides population estimates of the frequencies of HLA alleles at these eight loci in the three population groups, particularly for HLA-DPA1 and HLA-DPB1 that were not assayed in HapMap. Comparing between population-specific reference panels and a cosmopolitan panel created from all four HapMap populations, we demonstrate that more accurate imputation is obtained with population-specific panels than with the cosmopolitan panel, especially for the Malays and Indians but even when imputing between northern and southern Han Chinese. As with SNP imputation, common HLA alleles were imputed with greater accuracy than low-frequency variants.

To investigate the performance of laboratory methods and clinical case definitions in detecting the viral pathogens for acute respiratory infections (ARIs) from a prospective community cohort and hospital inpatients, nasopharyngeal swabs from cohort members reporting ARIs (community-ARI) and inpatients admitted with ARIs (inpatient-ARI) were tested by Singleplex Real Time-Polymerase Chain Reaction (SRT-PCR), multiplex RT-PCR (MRT-PCR) and pathogen-chip system (PathChip) between April 2012 and December 2013. Community-ARI and inpatient-ARI was also combined with mild and severe cases of influenza from a historical prospective study as mild-ARI and severe-ARI respectively to evaluate the performance of clinical case definitions. We analysed 130 community-ARI and 140 inpatient-ARI episodes (5 inpatient-ARI excluded because multiple pathogens were detected), involving 138 and 207 samples respectively. Detection by PCR declined with days post-onset for influenza virus; decrease was faster for community-ARI than for inpatient-ARI. No such patterns were observed for non-influenza respiratory virus infections. PathChip added substantially to viruses detected for community-ARI only. Clinical case definitions discriminated influenza from other mild-ARI but performed poorly for severe-ARI and for older participants. Rational strategies for diagnosis and surveillance of influenza and other respiratory virus must acknowledge the differences between ARIs presenting in community and hospital settings.

Background The collection of 24-h urine samples for the estimation of sodium intake is burdensome, and the utility of spot urine samples in Southeast Asian populations is unclear. Objective We aimed to assess the validity of prediction equations with the use of spot urine concentrations. Methods A sample of 144 Singapore residents of Chinese, Malay, and Indian ethnicity aged 18-79 y were recruited from the Singapore Health 2 Study conducted in 2014. Participants collected urine for 24 h in multiple small bottles on a single day. To determine the optimal collection time for a spot urine sample, a 1-mL sample was taken from a random bottle collected in the morning, afternoon, and evening. Published equations and a newly derived equation were used to predict 24-h sodium excretion from spot urine samples. Results The mean ± SD concentration of sodium from the 24-h urine sample was 125 ± 53.4 mmol/d, which is equivalent to 7.2 ± 3.1 g salt. Bland-Altman plots showed good agreement at the group level between estimated and actual 24-h sodium excretion, with biases for the morning period of -3.5 mmol (95% CI: -14.8, 7.8 mmol; new equation) and 1.46 mmol (95% CI: -10.0, 13.0 mmol; Intersalt equation). A larger bias of 25.7 mmol (95% CI: 12.2, 39.3 mmol) was observed for the Tanaka equation in the morning period. The prediction accuracy did not differ significantly for spot urine samples collected at different times of the day or at a random time of day (P = 0.11-0.76). Conclusion This study suggests that the application of both our own newly derived equation and the Intersalt equation to spot urine concentrations may be useful in predicting group means for 24-h sodium excretion in urban Asian populations.

Background In the context of a rapidly ageing population, Singapore is anticipating a rise in multimorbidity, disability, and dependency, which are driven by physical frailty. Healthy Older People Everyday (HOPE) is an epidemiologic population-based study on community-dwelling older adults aged 65 years and older in Singapore. Objective To investigate the prevalence of frail and prefrail states and their association with polypharmacy, multimorbidity, cognitive and functional status, and perceived health status among community-dwelling older adults in Singapore. Methods Participants for HOPE were older adults aged 65 years and older recruited from a cohort study on the northwest region of Singapore. Analysis was performed on data collected from a combination of interviewer-administered questionnaires (including FRAIL scale, EQ-5D, Mini Mental State Examination, Barthel index, and Lawton IADL scale), clinical assessments, and physical measurements (including hand grip strength and Timed-Up-and-Go [TUG] test). Results A total of 1051 older adults (mean age 71.2 years) completed the study. More than half (57.2%) were female. The prevalence of frailty and prefrailty was 6.2% and 37%, respectively. Frailty was associated with older age, female gender, Indian (instead of Chinese) ethnicity, multimorbidity, polypharmacy, cognitive and functional impairment, weaker hand grip strength, longer TUG times, and poor perceived health status. Those with underlying cognitive impairment and frailty were at greater risk of adverse health outcome. Conclusion Frailty is a complex health state with multiple domains and dimensions. In our study in a multiethnic Asian population, we identified nonmodifiable factors and modifiable risk factors (multimorbidity, polypharmacy, cognitive and functional impairment) that were associated with frailty. Interventions will have to be multipronged and will require a collaborated effort in order to effect change and improve the health span in rapidly ageing populations.

South Asia possesses a significant amount of genetic diversity due to considerable intergroup differences in culture and language. There have been numerous reports on the genetic structure of Asian Indians, although these have mostly relied on genotyping microarrays or targeted sequencing of the mitochondria and Y chromosomes. Asian Indians in Singapore are primarily descendants of immigrants from Dravidian-language–speaking states in south India, and 38 individuals from the general population underwent deep whole-genome sequencing with a target coverage of 30X as part of the Singapore Sequencing Indian Project (SSIP). The genetic structure and diversity of these samples were compared against samples from the Singapore Sequencing Malay Project and populations in Phase 1 of the 1,000 Genomes Project (1 KGP). SSIP samples exhibited greater intra-population genetic diversity and possessed higher heterozygous-to-homozygous genotype ratio than other Asian populations. When compared against a panel of well-defined Asian Indians, the genetic makeup of the SSIP samples was closely related to South Indians. However, even though the SSIP samples clustered distinctly from the Europeans in the global population structure analysis with autosomal SNPs, eight samples were assigned to mitochondrial haplogroups that were predominantly present in Europeans and possessed higher European admixture than the remaining samples. An analysis of the relative relatedness between SSIP with two archaic hominins (Denisovan, Neanderthal) identified higher ancient admixture in East Asian populations than in SSIP. The data resource for these samples is publicly available and is expected to serve as a valuable complement to the South Asian samples in Phase 3 of 1 KGP., Author Summary Indians of South Asia has long been a population of interest to a wide audience, due to its unique diversity. We have deep-sequenced 38 individuals of Indian descent residing in Singapore (SSIP) in an effort to illustrate their diversity from a whole-genome standpoint. Indeed, among Asians in our population panel, SSIP was most diverse, followed by the Malays in Singapore (SSMP). Their diversity is further observed in the population's chromosome Y haplogroup and mitochondria haplogroup profiles; individuals with European-dominant haplogroups had greater proportion of European admixture. Among variants (single nucleotide polymorphism and small insertions/deletions) discovered in SSIP, 21.69% were novel with respect to previous sequencing projects. In addition, some 14 loss-of-function variants (LOFs) were associated to cancer, Type II diabetes, and cholesterol levels. Finally, D statistic test with ancient hominids concurred that there was gene flow to East Asians compared to South Asians.