Development and validation of a lifestyle risk index to screen for metabolic syndrome and its components in two multi-ethnic cohorts.

BACKGROUND: Metabolic syndrome (MetS) is a precursor to cardiovascular diseases and type 2 diabetes. Existing MetS prediction models relied heavily on biochemical measures and those based on non-invasive predictors such as lifestyle behaviours were limited. We aim to (1) develop a weighted lifestyle risk index for MetS and (2) externally validate this index using two Asian-based cohorts in Singapore. METHODS: Using data from the Multi-Ethnic Cohort (MEC) 1 (n = 2873, 41% male), multiple logistic regression was used to identify predictors associated with MetS. A weighted lifestyle risk index was generated using coefficients of the selected predictors in the development cohort (MEC1). Subsequently, the performance of the lifestyle risk index in predicting the occurrence of MetS within 10 years was assessed by discrimination and calibration in an external validation cohort (MEC2) (n = 6070, 43% male). RESULTS: A lifestyle risk index for MetS with nine predictors was developed (age, sex, ethnicity, having a family history of diabetes, BMI, diet, physical activity, smoking status, and screen time). This index demonstrated acceptable discrimination in the development cohort [AUC (95% CI) = 0.74 (0.71, 0.76)] and the validation cohort [AUC (95% CI) = 0.79 (0.77, 0.81)]. CONCLUSION: This lifestyle risk index exhibits potential for risk stratification in population-based screening programmes. Future research could apply a similar methodology to develop disease-specific lifestyle risk indices using nationwide registry-based data.

Value of a UK medical degree for international students (VISION): a cross-sectional study.

OBJECTIVES: It is estimated that NHS staff consist of over 200 different nationalities, with a reported 30.7% of doctors holding a nationality other than British. Despite this, international medical students represent 7.5% of all medical students studying in the UK and pay on average, 4-6 times more in tuition fees when compared with the £9250 per annum (Great British Pounds (£) in 2021) paid by home students. This study's aim and objective are to evaluate the perception of the financial cost and value of the UK medical degree for international students and their motivations for pursuing such a degree. METHODS: This is a cross-sectional observational study enquiring about international premedical, medical and medical school graduates' perception of the value of the UK medical degree and factors influencing their decision to study in the UK.A questionnaire was developed and distributed to 24 medical schools and 64 secondary schools both internationally and across the UK. RESULTS: A total of 352 responses from 56 nationalities were recorded. 96% of international students identified clinical and academic opportunities as the most important factors to study medicine in the UK, closely followed by quality of life (88%). The least important factor was family reasons, with 39% of individuals identifying this factor. Only 4.82% of graduates in our study considered leaving the UK after training. Overall, 54% of students felt the UK degree was value for money. This belief was significantly higher in premedical students compared with existing students and graduates (71% vs 52% and 20%, p<0.001 for all comparisons). CONCLUSION: The quality of medical education and international prestige are attractive factors for international students to study medicine in the UK. However, further work is needed to ascertain reasons for the differing perceptions of the value by international students at different stages in their clinical training.

Nutrient trajectories during infancy and their associations with childhood neurodevelopment.

PURPOSE: To examine the associations between infants' dietary nutrient trajectories and subsequent neurodevelopment during childhood in the Growing Up in Singapore Towards healthy Outcomes study. METHODS: One-day food records were collected at ages 6, 9 and 12 months, whilst Bayley Scales of Infant and Toddler Development-III and Kaufman Brief Intelligence Test-2 were conducted at ages 24 and 54 months respectively. Nutrient trajectories were constructed using multi-level mixed modelling and associations with neurodevelopment (24 months: n = 484; 54 months: n = 444) were examined using adjusted multivariable linear regression. RESULTS: At age 24 months, higher protein intake (at 6 months) and increasing rate of intake (from 6 to 12 months) were associated with higher fine motor score [ß = 0.17 SD (95% CI 0.03, 0.31) and 0.62 SD (0.10, 1.14) respectively]. Higher fat intake was associated with higher receptive language score [0.04 SD (0.003, 0.07)], but increasing rate of intake was associated with lower expressive language [- 0.20 SD (- 0.39, - 0.01)] and fine motor [- 0.29 SD (- 0.48, - 0.10)] scores. Higher carbohydrate intake was associated with lower gross motor score [- 0.07 SD (- 0.14, - 0.005)], but increasing rate of intake was associated with higher receptive language [0.44 SD (0.08, 0.81)] and fine motor [0.56 SD (0.18, 0.93)] scores. Increasing rate of dietary fibre intake was associated with higher fine motor scores [0.63 SD (0.16, 1.10)]. No significant associations were observed with neurodevelopment at 54 months. CONCLUSION: Our findings provide greater understanding of how nutrition over time could have varying effects on child neurodevelopment.

Modifiable Risk Factor Score and Fecundability in a Preconception Cohort in Singapore.

Importance: Although multiple modifiable risk factors have been identified for reduced fecundability (defined as lower probability of conception within a menstrual cycle), no scoring system has been established to systematically evaluate fecundability among females who are attempting to conceive. Objective: To examine the association of a risk score based on 6 modifiable factors with fecundability, and to estimate the percentage reduction in incidence of nonconception if all study participants achieved a minimal risk score level. Design, Setting, and Participants: This population-based cohort study obtained data from the S-PRESTO (Singapore Preconception Study of Long-Term Maternal and Child Outcomes) prospective cohort study. Females of reproductive age who were trying to conceive were enrolled from February 2015 to October 2017 and followed for 1 year, ending in November 2018. Data were analyzed from March to May 2022. Exposures: A reduced fecundability risk score was derived by giving participants 1 point for each of the following factors: unhealthy body mass index, unhealthy diet, smoking, alcohol intake, folic acid supplement nonuser, and older maternal age. Total scores ranged from 0 to 6 and were classified into 5 levels: level 1 (score of 0 or 1), level 2 (score of 2), level 3 (score of 3), level 4 (score of 4), and level 5 (score of 5 or 6). Main Outcomes and Measures: Fecundability, measured by time to conception in cycles, was analyzed using discrete-time proportional hazards models with confounder adjustment. Results: A total of 937 females (mean [SD] age, 30.8 [3.8] years) were included, among whom 401 (42.8%) spontaneously conceived within 1 year of attempting conception; the median (IQR) number of cycles before conception was 4 (2-7). Compared with participants with a level 1 risk score, those with level 2, 3, 4, and 5 risk scores had reductions in fecundability of 31% (adjusted fecundability ratio [FR], 0.69; 95% CI, 0.54-0.88), 41% (FR, 0.59; 95% CI, 0.45-0.78), 54% (FR, 0.46; 95% CI, 0.31-0.69) and 77% (FR, 0.23; 95% CI, 0.07-0.73), respectively. Assessment of the population attributable fraction showed that all participants achieving a minimal (level 1) risk level would be associated with a reduction of 34% (95% CI, 30%-39%) in nonconception within a year. Conclusions and Relevance: Results of this study revealed the co-occurrence of multiple modifiable risk factors for lowered fecundability and a substantially higher conception rate among participants with no or minimal risk factors. The risk assessment scoring system proposed is a simple and potentially useful public health tool for mitigating risks and guiding those who are trying to conceive.

Dietary Supplement Intake and Fecundability in a Singapore Preconception Cohort Study.

Subfertility is a global problem affecting millions worldwide, with declining total fertility rates. Preconception dietary supplementation may improve fecundability, but the magnitude of impact remains unclear. This prospective cohort study aimed to examine the association of preconception micronutrient supplements with fecundability, measured by time to pregnancy (TTP). The study was conducted at KK Women's and Children's Hospital, Singapore, between February 2015 and October 2017, on 908 women aged 18-45 years old, who were trying to conceive and were enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO). Baseline sociodemographic characteristics and supplement intake were collected through face-to-face interviews. The fecundability ratio (FR) was estimated using discrete-time proportional hazard modelling. Adjusting for potentially confounding variables, folic acid (FA) (FR 1.26, 95% confidence interval 1.03-1.56) and iodine (1.28, 1.00-1.65) supplement users had higher fecundability compared to non-users. Conversely, evening primrose oil supplement users had lower fecundability (0.56, 0.31-0.99) than non-users. In this study, preconception FA and iodine supplementation were associated with shortened TTP, while evening primrose oil use was associated with longer TTP. Nonetheless, the association between supplement use and the magnitude of fecundability changes will need to be further confirmed with well-designed randomised controlled trials.

Protist.guru: A Comparative Transcriptomics Database for Protists.

During the last few decades, the study of microbial ecology has been enabled by molecular and genomic data. DNA sequencing has revealed the surprising extent of microbial diversity and how microbial processes run global ecosystems. However, significant gaps in our understanding of the microbial world remain, and one example is that microbial eukaryotes, or protists, are still largely neglected. To address this gap, we used gene expression data from 17 protist species to create protist.guru: an online database equipped with tools for identifying co-expressed genes, gene families, and co-expression clusters enriched for specific biological functions. Here, we show how our database can be used to reveal genes involved in essential pathways, such as the synthesis of secondary carotenoids in Haematococcus lacustris. We expect protist.guru to serve as a valuable resource for protistologists, as well as a catalyst for discoveries and new insights into the biological processes of microbial eukaryotes. AVAILABILITY: The database and co-expression networks are freely available from http://protist.guru/. The expression matrices and sample annotations are found in the supplementary data.

Upper limb infections: A comparison between diabetic and non-diabetic patients.

BACKGROUND: Upper limb infections are common among patients with diabetes mellitus and their sequelae can be debilitating. They tend to present with severe infections but minimal symptoms probably due to neuropathy and vasculopathy among diabetics. The study aims to compare the demographic characteristics, clinical presentations and outcomes of upper limb infections between diabetic and non-diabetic patients. METHODS: All patients with upper limb infections who were admitted in a tertiary hospital from June 2017 to December 2020 were included in this study. Demographic data, clinical presentations, investigations and outcomes were obtained retrospectively from electronic medical record. There were 117 patients with diabetes mellitus and 127 with no diabetes mellitus. Comparisons were made between these two groups, and statistical analysis was done with SPSS. RESULTS: There were 244 patients included; 117 were diabetic and 127 were non-diabetic. Diabetic patients were more likely to present with emergent scenarios, especially necrotizing fasciitis and infective tenosynovitis (p < .05) with higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) readings (p < .05). Their microbiological cultures were less likely to be negative (p < .05). Diabetic patients also had poorer clinical outcomes with higher risk of amputation, re-operation and longer duration of hospital stay (p < .05). CONCLUSION: Upper limb infections among diabetic patients should be treated aggressively. Early diagnosis and surgical intervention might decrease the morbidity and mortality in this group. Prevention of infections should be emphasized.

Prepregnancy adherence to plant-based diet indices and exploratory dietary patterns in relation to fecundability.

BACKGROUND: Modest associations have been reported between specific food groups or nutrients and fecundability [measured by time to pregnancy (TTP)]. Examining overall diets provides a more holistic approach towards understanding their associations with fecundability. It is not known whether plant-based diets indices or exploratory dietary patterns are associated with fecundability. OBJECTIVES: We examine the associations between adherence to 1) plant-based diet indices; and 2) exploratory dietary patterns and fecundability among women planning pregnancy. METHODS: Data were analyzed from the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. Prepregnancy diet was assessed using a semi-quantitative FFQ from which the overall, healthful, and unhealthful plant-based diet indices (oPDI, hPDI, and uPDI, respectively) were calculated. Exploratory dietary patterns were derived using factor analysis based on 44 predefined food groups. Participants were categorized into quintiles based on their dietary pattern scores. TTP (expressed in menstrual cycles) was ascertained within a year from the prepregnancy dietary assessment. Discrete-time proportional hazard models, adjusted for confounders, were used to estimate fecundability ratios (FRs) and 95% CIs, with FR > 1 indicating a shorter TTP. RESULTS: Among 805 women, 383 pregnancies were confirmed by ultrasound scans. Compared with women in the lowest quintile, those in the highest quintile of the uPDI had reduced fecundability (FR of Q5 compared with Q1, 0.65; 95% CI, 0.46-0.91; P trend, 0.009). Conversely, greater adherence to the hPDI was associated with increased fecundability (1.46; 95% CI, 1.02-2.07; P trend, 0.036). The oPDI was not associated with fecundability. Among the 3 exploratory dietary patterns, only greater adherence to the Fast Food and Sweetened Beverages (FFSB) pattern was associated with reduced fecundability (0.61; 95% CI, 0.40-0.91; P trend, 0.018). CONCLUSIONS: Greater adherence to the uPDI or the FFSB dietary pattern was associated with reduced fecundability among Asian women. Greater adherence to the hPDI may be beneficial for fecundability, though this requires confirmation by future studies.

Evaluation of Preconception Dietary Patterns in Women Enrolled in a Multisite Study.

Background: Diet indices are widely used in nutritional research across communities but do not "capture" the full extent of diet variability across multiple countries. Empirically derived dietary patterns can provide additional information because they reflect combinations of foods potentially associated with health outcomes. Limited studies have evaluated preconception dietary patterns in heterogeneous populations. Objectives: In the multisite Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR) study, the secondary aims included: 1) derive pooled and site-specific preconception dietary patterns, and 2) evaluate these patterns using anthropometric measures and metabolic biomarkers. Methods: Women planning pregnancy (n = 1720) in the United Kingdom, Singapore, and New Zealand completed interviewer-administered harmonized FFQs and lifestyle questionnaires at recruitment. Across-cohort ("pooled") and site-specific dietary patterns were derived, and associations between dietary pattern scores and BMI, waist-to-hip ratio, plasma lipids, and glycemia assessed using multivariable linear regression, expressing results as SD change in outcome per SD change in dietary pattern score. Results: The pooled analysis identified 3 dietary patterns: "Vegetables/Fruits/Nuts" ("Healthy"), "Fried potatoes/Processed meat/Sweetened beverages" ("Less Healthy"), and "Fish/Poultry/Noodles/Rice" ("Mixed"). The "Healthy" and "Less Healthy" pooled pattern scores were highly correlated with their corresponding site-specific dietary pattern scores ("Healthy": ρ = 0.87-0.93; "Less Healthy": ρ = 0.65-0.88). Women with higher scores for the "Healthy" pooled pattern had a lower waist-to-hip ratio (standardized ß: -0.10; 95% CI: -0.18, -0.01); those with higher scores for the "Less Healthy" pooled pattern had a higher BMI (standardized ß: 0.17; 95% CI: 0.09, 0.24), higher LDL cholesterol (standardized ß: 0.10; 95% CI: 0.01, 0.19), and less optimal glucose profiles. However, we noted higher adherence to the "Healthy" pooled pattern with higher BMI. Conclusions: The "Healthy" and "Less Healthy" pooled patterns were comparable to the corresponding site-specific patterns. Although the associations between these patterns and objective anthropometric/metabolic measures were largely in the expected directions, future studies are required to confirm these findings.This trial is registered at clinicaltrials.gov (NCT02509988).

Identification and reproducibility of dietary patterns assessed with a FFQ among women planning pregnancy.

OBJECTIVE: To identify a posteriori dietary patterns among women planning pregnancy and assess the reproducibility of these patterns in a subsample using two dietary assessment methods. DESIGN: A semi-quantitative FFQ was administered to women enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes study. Dietary patterns from the FFQ were identified using exploratory factor analysis (EFA). In a subsample of women (n 289), 3-d food diaries (3DFD) were also completed and analysed. Reproducibility of the identified patterns was assessed using confirmatory factor analysis (CFA) in the subsample, and goodness of fit of the CFA models was examined using several fit indices. Subsequently, EFA was conducted in the subsample and dietary patterns of the FFQ and the 3DFD were compared. SETTING: Singapore. PARTICIPANTS: 1007 women planning pregnancy (18-45 years). RESULTS: Three dietary patterns were identified from the FFQ: the 'Fish, Poultry/Meat and Noodles' pattern was characterised by higher intakes of fish, poultry/meat and noodles in soup; 'Fast Food and Sweetened Beverages' pattern was characterised by higher intakes of fast food, sweetened beverages and fried snacks; 'Bread, Legumes and Dairy' pattern was characterised by higher intakes of buns/ethnic breads, nuts/legumes and dairy products. The comparative fit indices from the CFA models were 0·79 and 0·34 for the FFQ and 3DFD of the subsample, respectively. In the subsample, three similar patterns were identified in the FFQ while only two for the 3DFD. CONCLUSIONS: Dietary patterns from the FFQ are reproducible within this cohort, providing a basis for future investigations on diet and health outcomes.

Fungi.guru: Comparative genomic and transcriptomic resource for the fungi kingdom.

The fungi kingdom is composed of eukaryotic heterotrophs, which are responsible for balancing the ecosystem and play a major role as decomposers. They also produce a vast diversity of secondary metabolites, which have antibiotic or pharmacological properties. However, our lack of knowledge of gene function in fungi precludes us from tailoring them to our needs and tapping into their metabolic diversity. To help remedy this, we gathered genomic and gene expression data of 19 most widely-researched fungi to build an online tool, fungi.guru, which contains tools for cross-species identification of conserved pathways, functional gene modules, and gene families. We exemplify how our tool can elucidate the molecular function, biological process and cellular component of genes involved in various biological processes, by identifying a secondary metabolite pathway producing gliotoxin in Aspergillus fumigatus, the catabolic pathway of cellulose in Coprinopsis cinerea and the conserved DNA replication pathway in Fusarium graminearum and Pyricularia oryzae. The tool is available at www.fungi.guru.

Assessment of aPTT-based clot waveform analysis for the detection of haemostatic changes in different types of infections.

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p < 0.001), with the mean (± SD) aPTT longest in dengue infection (n = 36) (37.99 ± 7.93 s), followed by bacterial infection (n = 52) (33.96 ± 7.33 s) and respiratory viral infection (n = 13) (29.98 ± 3.92 s). Compared to controls (min1; min2; max2) (5.53 ± 1.16%/s; 0.89 ± 0.19%/s2; 0.74 ± 0.16%/s2), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s2; 0.82 ± 0.24%/s2, all p < 0.05); dengue infection has significantly lower CWA values (3.93 ± 1.32%/s; 0.57 ± 0.17%/s2; 0.43 ± 0.14%/s2, all p < 0.001) whilst respiratory virus infection has similar results (6.19 ± 1.32%/s; 0.95 ± 0.21%/s2; 0.73 ± 0.18%/s2, all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p < 0.01). Different infections affect CWA distinctively. CWA could provide information on the haemostatic milieu triggered by infection and further studies are needed to better define its application in this area.

Food Sources of Energy and Macronutrient Intakes among Infants from 6 to 12 Months of Age: The Growing Up in Singapore Towards Healthy Outcomes (GUSTO) Study.

Adequate nutrition during complementary feeding is important for the growth, development and well-being of children. We aim to examine the energy and macronutrient intake composition and their main food sources in a mother-offspring cohort study in Singapore. The diets of infants were assessed by 24 h dietary recalls or food diaries collected from mothers when their offspring were 6 (n = 760), 9 (n = 893) and 12 (n = 907) months of age. Food sources of energy and macronutrients were determined using the population proportion methodology. Energy intakes per day (kcal; mean (standard deviation, SD)) of these infants were 640 (158) at 6 months, 675 (173) at 9 months, and 761 (208) at 12 months. Infant formula, breastmilk and infant cereals were the top three food sources of energy and macronutrient intakes in infants through the period 6 to 12 months. Other main energy and carbohydrate sources at 9 and 12 months of age were rice porridge, infant biscuits and fresh fruits, while fish, red meat and eggs were the other main protein and total fat sources. Breast-fed and mixed-fed infants had a more varied diet as compared to formula-fed infants. Formula-fed infants had consistently higher protein and lower total fat consumption compared to those who were breastfed. An understanding of these main food sources during complementary feeding can inform local dietary recommendations and policies.

Impact of postgrafting immunosuppressive regimens on nonrelapse mortality and survival after nonmyeloablative allogeneic hematopoietic stem cell transplant using the fludarabine and low-dose total-body irradiation 200-cGy.

The development of nonmyeloablative (NM) hematopoietic cell transplantation (HCT) has extended the potential curative treatment option of allografting to patients in whom it was previously contraindicated because of advanced age or comorbidity. Acute and chronic graft versus host disease (GVHD) and its consequent nonrelapse mortality (NRM), remains the major limitation of NM HCT. In this report, we analyzed the outcome of 67 patients (median age, 45 years) with hematologic diseases receiving NM conditioning with fludarabine 90 mg/m(2) and total body irradiation (TBI) 200-cGy, followed by filgrastim-mobilized peripheral blood stem cell transplant from HLA identical (n = 61), 5/6 antigen-matched related (n = 1), 6/6 antigen-matched unrelated (n = 3), and 5/6 antigen-matched unrelated (n = 2) donors. The first cohort of 21 patients were given cyclosporine (CSP) and mycophenolate mofetil (MMF) as postgrafting immunosuppression, whereas the subsequent cohort was given additional methotrexate (MTX) and extended duration of CSP/MMF prophylaxis in an attempt to reduce graft-versus-host disease (GVHD). Sixty-four (95%) patients engrafted and 3 (5%) had secondary graft failure. Myelosuppression was moderate with neutrophil counts not declining below 500/microL in approximately 25% of patients, and with more than half of the patients not requiring any blood or platelet transfusion. The 2-year cumulative interval (CI) of grade II-IV, grade III-IV acute GVHD and chronic GVHD were 49%, 30%, and 34%, respectively. The 2-year probability of NRM, overall (OS), and progression-free (PFS) survival were 27%, 43%, and 28%, respectively. GVHD-related death accounted for 85% of NRM. Compared with patients receiving CSP/MMF, patients receiving extended duration of CSP/MMF with additional MTX in postgrafting immunosuppression had a significantly lower risk of grade III-IV acute GVHD (CI 20% versus 52%; P = .009) and NRM (CI at 2 years: 11% versus 62%; P < .001), without any significant adverse impact on the risk of relapse (CI at 2 years: 59% versus 33%; P = .174) Subgroup analysis of a cohort of patients given MTX/CSP/MMF showed that patients with "standard risk" diseases (n = 21) had a 3-year OS and PFS of 85% and 65%, respectively. This compares favorably to the 41% (P = .02) and 23% (P = .03) OS and PFS, respectively, in patients with "high-risk" diseases (n = 25). In conclusion, the addition of MTX onto the current postgrafting immunosuppression regimen with extended CSP/MMF prophylaxis duration provides more effective protection against severe GVHD, and is associated with more favorable outcome in patients receiving NM fludarabine/TBI conditioning than in patients receiving fludarabine/TBI conditioning with CSP and MMF without MTX.