Hiromi Koh

Amount, type, and sources of carbohydrates in relation to ischemic heart disease mortality in a Chinese population: a prospective cohort study

BACKGROUND The relation between carbohydrate intake and risk of ischemic heart disease (IHD) has not been fully explored in Asian populations known to have high-carbohydrate diets. OBJECTIVE We assessed whether intakes of total carbohydrates, different types of carbohydrates, and their food sources were associated with IHD mortality in a Chinese population. DESIGN We prospectively examined the association of carbohydrate intake and IHD mortality in 53,469 participants in the Singapore Chinese Health Study with an average follow-up of 15 y. Diet was assessed by using a semiquantitative food-frequency questionnaire. HRs and 95% CIs were calculated by using a Cox proportional hazards analysis. RESULTS We documented 1660 IHD deaths during 804,433 person-years of follow-up. Total carbohydrate intake was not associated with IHD mortality risk [men: HR per 5% of energy, 0.97 (95% CI: 0.92, 1.03); women: 1.06 (95% CI: 0.99, 1.14)]. When types of carbohydrates were analyzed individually, starch intake was associated with higher risk [men: 1.03 (95% CI: 0.99, 1.08); women: 1.08, (95% CI: 1.02, 1.14)] and fiber intake with lower risk of IHD mortality [men: 0.94 (95% CI: 0.82, 1.08); women: 0.71 (95% CI: 0.60, 0.84)], with stronger associations in women than men (both P-interaction < 0.01). In substitution analyses, the replacement of one daily serving of rice with one daily serving of noodles was associated with higher risk (difference in HR: 26.11%; 95% CI: 10.98%, 43.30%). In contrast, replacing one daily serving of rice with one of vegetables (-23.81%; 95% CI: -33.12%, -13.20%), fruit (-11.94%; 95% CI: -17.49%, -6.00%), or whole-wheat bread (-19.46%; 95% CI: -34.28%, -1.29%) was associated with lower risk of IHD death. CONCLUSIONS In this Asian population with high carbohydrate intake, the total amount of carbohydrates consumed was not substantially associated with IHD mortality. In contrast, the shifting of food sources of carbohydrates toward a higher consumption of fruit, vegetables, and whole grains was associated with lower risk of IHD death.

Factors influencing infection by pandemic influenza A(H1N1)pdm09 over three epidemic waves in Singapore

Previous influenza pandemics had second and on occasion third waves in many countries that were at times more severe than the initial pandemic waves.

Plasma fatty acids, oxylipins, and risk of myocardial infarction: the Singapore Chinese Health Study

We aimed to examine the prospective association between plasma FAs, oxylipins, and risk of acute myocardial infarction (AMI) in a Singapore Chinese population. A nested case-control study with 744 incident AMI cases and 744 matched controls aged 47–83 years was conducted within the Singapore Chinese Health Study. Nineteen plasma FAs and 12 oxylipins were quantified using MS. These were grouped into 12 FA clusters and 5 oxylipin clusters using hierarchical clustering, and their associations with AMI risk were assessed. Long-chain n-3 FAs [odds ratio (OR) = 0.67 per SD increase, 95% confidence interval (CI): 0.53–0.84, P < 0.001] and stearic acid (OR = 0.65, 95% CI: 0.44–0.97, P = 0.03) were inversely associated with AMI risk, whereas arachidonic acid (AA) was positively associated with AMI risk (OR = 1.25, 95% CI: 1.03–1.52, P = 0.02) in the multivariable model with adjustment for other FAs. Further adjustment for oxylipins did not substantially change these associations. An inverse association was observed between AA-derived oxylipin, thromboxane (TX)B2, and AMI risk (OR = 0.81, 95% CI: 0.71–0.93, P = 0.003). Circulating long-chain n-3 FAs and stearic acid were associated with a lower and AA was associated with a higher AMI risk in this Chinese population. The association between the oxylipin TXB2 and AMI requires further research.

The Pittsburgh Sleep Quality Index in a multi-ethnic Asian population contains a three-factor structure

PurposeThe Pittsburgh Sleep Quality Index (PSQI) is a widely used measure for assessing sleep impairment. Although it was developed as a unidimensional instrument, there is much debate that it contains multidimensional latent constructs. We examined the dimensionality of the underlying factor structure of PSQI in Singapore, a rapidly industrialising Asian country with multi-ethnicities representing the Chinese, Malays and Indians.MethodsThe PSQI was administered through an interviewer-based questionnaire in two separate population-based cross-sectional surveys. An explanatory factor analysis (EFA) was first used to explore the underlying construct of the PSQI in both studies. Then, a confirmatory factor analysis (CFA) was conducted to evaluate an optimal factor model by comparing against other possible models identified in EFA.ResultsThere are three correlated yet distinguishable factors that account for an individual’s sleep experience from the same best-fit model obtained in both studies: perceived sleep quality, daily disturbances and sleep efficiency. Our three-factor structure of PSQI is superior to the originally intended unidimensional model. Our model also shows the best-fit indices when compared to the previously reported single-factor, two-factor and three-factor (by Cole et al.) models in a multi-ethnic Asian population.ConclusionThere is strong evidence that the PSQI contains a three-factor rather than a unidimensional structure in a multi-ethnic Asian population. Scoring the PSQI along their multidimensional perspectives may provide a more accurate understanding of the relationship between sleep impairment and health conditions rather than using a single global score.

EBprot: Statistical analysis of labeling-based quantitative proteomics data.

Labeling‐based proteomics is a powerful method for detection of differentially expressed proteins (DEPs). The current data analysis platform typically relies on protein‐level ratios, which is obtained by summarizing peptide‐level ratios for each protein. In shotgun proteomics, however, some proteins are quantified with more peptides than others, and this reproducibility information is not incorporated into the differential expression (DE) analysis. Here, we propose a novel probabilistic framework EBprot that directly models the peptide‐protein hierarchy and rewards the proteins with reproducible evidence of DE over multiple peptides. To evaluate its performance with known DE states, we conducted a simulation study to show that the peptide‐level analysis of EBprot provides better receiver‐operating characteristic and more accurate estimation of the false discovery rates than the methods based on protein‐level ratios. We also demonstrate superior classification performance of peptide‐level EBprot analysis in a spike‐in dataset. To illustrate the wide applicability of EBprot in different experimental designs, we applied EBprot to a dataset for lung cancer subtype analysis with biological replicates and another dataset for time course phosphoproteome analysis of EGF‐stimulated HeLa cells with multiplexed labeling. Through these examples, we show that the peptide‐level analysis of EBprot is a robust alternative to the existing statistical methods for the DE analysis of labeling‐based quantitative datasets. The software suite is freely available on the Sourceforge website http://ebprot.sourceforge.net/. All MS data have been deposited in the ProteomeXchange with identifier PXD001426 (http://proteomecentral.proteomexchange.org/dataset/PXD001426/).

SAINTq: Scoring protein-protein interactions in affinity purification - mass spectrometry experiments with fragment or peptide intensity data.

SAINT (Significance Analysis of INTeractome) is a probabilistic method for scoring bait‐prey interactions against negative controls in affinity purification – mass spectrometry (AP‐MS) experiments. Our published SAINT algorithms use spectral counts or protein intensities as the input for calculating the probability of true interaction, which enables objective selection of high‐confidence interactions with false discovery control. With the advent of new protein quantification methods such as Data Independent Acquisition (DIA), we redeveloped the scoring method to utilize the reproducibility information embedded in the peptide or fragment intensity data as a key scoring criterion, bypassing protein intensity summarization required in the previous SAINT workflow. The new software package, SAINTq, addresses key issues in the interaction scoring based on intensity data, including treatment of missing values and selection of peptides and fragments for scoring each prey protein. We applied SAINTq to two independent DIA AP‐MS data sets profiling the interactome of MEPCE and EIF4A2 and that of 14‐3‐3β, and benchmarked the performance in terms of recovering previously reported literature interactions in the iRefIndex database. In both data sets, the SAINTq analysis using the fragment‐level intensity data led to the most sensitive detection of literature interactions at the same level of specificity. This analysis outperforms the analysis using protein intensity data summed from fragment intensity data that is equivalent to the model in SAINTexpress.

Development of a Semi-Quantitative Food Frequency Questionnaire to Assess the Dietary Intake of a Multi-Ethnic Urban Asian Population

Assessing habitual food consumption is challenging in multi-ethnic cosmopolitan settings. We systematically developed a semi-quantitative food frequency questionnaire (FFQ) in a multi-ethnic population in Singapore, using data from two 24-h dietary recalls from a nationally representative sample of 805 Singapore residents of Chinese, Malay and Indian ethnicity aged 18–79 years. Key steps included combining reported items on 24-h recalls into standardized food groups, developing a food list for the FFQ, pilot testing of different question formats, and cognitive interviews. Percentage contribution analysis and stepwise regression analysis were used to identify foods contributing cumulatively ≥90% to intakes and individually ≥1% to intake variance of key nutrients, for the total study population and for each ethnic group separately. Differences between ethnic groups were observed in proportions of consumers of certain foods (e.g., lentil stews, 1%–47%; and pork dishes, 0%–50%). The number of foods needed to explain variability in nutrient intakes differed substantially by ethnic groups and was substantially larger for the total population than for separate ethnic groups. A 163-item FFQ covered >95% of total population intake for all key nutrients. The methodological insights provided in this paper may be useful in developing similar FFQs in other multi-ethnic settings.

Ikk2 regulates cytokinesis during vertebrate development

NFκB signaling has a pivotal role in regulation of development, innate immunity, and inflammation. Ikk2 is one of the two critical kinases that regulate the NFκB signaling pathway. While the role of Ikk2 in immunity, inflammation and oncogenesis has received attention, an understanding of the role of Ikk2 in vertebrate development has been compounded by the embryonic lethality seen in mice lacking Ikk2. We find that despite abnormal angiogenesis in IKK2 zygotic mutants of zebrafish, the maternal activity of Ikk2 supports embryogenesis and maturation of fertile animals and allows to study the role of IKK2 in development. Maternal-zygotic ikk2 mutants represent the first vertebrates globally devoid of maternal and zygotic Ikk2 activity. They are defective in cell proliferation as evidenced by abnormal cytokinesis, nuclear enlargement and syncytialisation of a significant portion of blastoderm. We further document that reduced phosphorylation of Aurora A by Ikk2 could underlie the basis of these defects in cell division.