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Background: While healthy dietary and lifestyle factors have been individually linked to lower colorectal cancer (CRC) risks, recommendations for whole diet-lifestyle patterns remained unestablished due to limited studies and inconsistent pattern definitions., Objective: This updated review synthesized literature on dietary-lifestyle patterns and CRC risk/mortality., Methods: PubMed and Embase were searched through 31 March 2023 for randomized controlled trials and prospective cohort studies examining adulthood dietary patterns combined with modifiable lifestyle factors such as adiposity, smoking, alcohol consumption, physical activity, and/or others. Patterns were categorized by derivation methods: a priori, a posteriori, and a hybrid combining both; and were then descriptively reviewed for the primary outcomes: CRC risk or mortality. The Global Cancer Update Programme Expert Committee and Expert Panel independently graded the evidence on the likelihood of causality using pre-defined grading criteria., Results: Thirty-three observational studies were reviewed. 'Strong-probable' evidence was concluded for higher levels of alignment with the a priori-derived World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations score and lower CRC risk; and 'limited-suggestive' evidence for the American Cancer Society guidelines and Healthy Lifestyle Index with lower CRC risk (mainly due to concerns about risk of bias for confounding). A posteriori-derived patterns lack firm evidence (only one study). 'Strong-probable' evidence was concluded for higher levels of alignment with the Empirical Lifestyle Index for Hyperinsulinemia hybrid pattern and higher CRC risk. By cancer subsite, only the WCRF/AICR recommendations score showed 'strong-probable' evidence with lower colon cancer risk. All exposure-mortality pairs were graded 'limited-no conclusion'. The evidence for other pattern-outcome associations was graded as 'limited-no conclusion'., Conclusions: Adopting a healthy pattern of diet, maintaining a healthy weight, staying physically active, and embracing health-conscious habits, such as avoiding tobacco and moderating alcohol, are collectively associated with a lower CRC risk. Healthy lifestyle habits are key to primary CRC prevention., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests. IARC disclaimer: Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., (Copyright © 2025. Published by Elsevier Inc.)

Background: Physical activity (PA), sedentary behavior (SB), and sleep are collectively referred to as 24-h movement behaviors, which may be linked to cognitive development in children. However, most of the evidence was based on cross-sectional studies and/or solely relied on parent-reported information on children's behaviors, and it remains uncertain whether all domains/contexts of PA and SB are similarly associated with executive function and academic achievement., Objective: We investigated the prospective associations of accelerometer-measured 24 h-movement behaviors and domain-specific PA and SB with executive function and academic achievement among school-aged children in Singapore., Methods: The Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort used a wrist-worn accelerometer (Actigraph-GT3x+) to measure 24 h-movement behaviors data at ages 5.5 and 8 years. Executive function and academic achievement were assessed using NEuroPSYchology (NEPSY) and Wechsler Individual Achievement Tests at ages 8.5 and 9-years, respectively. Compositional data analyses were conducted to explore the associations of 24 h-movement behavior with outcomes, and multiple linear regression models to examine the associations of domain-specific PA and SB with outcomes ( n  = 432)., Results: Among 432 children whose parents agreed to cognitive assessments (47% girls and 58% Chinese), the composition of 24 h-movement behaviors at ages 5.5 and 8 years was not associated with executive function and academic achievement. However, higher moderate-to-vigorous PA (MVPA) relative to remaining movement behaviors at age 5.5 years was associated with lower academic achievement [Mean difference (95% confidence interval): -0.367 (-0.726, -0.009) z-score], and reallocating MVPA time to sleep showed higher academic achievement scores [30 min from MVPA to sleep: 0.214 (0.023, 0.404) z-score]. Certain domains of PA and SB, notably organized PA/sports, outdoor play, and reading books were favorably associated with outcomes of interest, while indoor play and screen-viewing were unfavorably associated., Conclusion: The associations between movement behaviors and cognitive outcomes are multifaceted, influenced by specific domains of PA and SB. This study underscores the importance of participation in organized PA/sports, outdoor active play, and reading books, while ensuring adequate sleep and limiting screen viewing, to enhance cognitive outcomes. These findings underscore the need for further research into time-use trade-offs. Such studies could have major implications for revising current guidelines or strategies aimed at promoting healthier 24 h-movement behaviors in children., Study Registration: https://clinicaltrials.gov/, NCT01174875., Competing Interests: KMG receiving reimbursement for speaking at conferences sponsored by companies selling nutritional products. KMG and S-YC report being part of an academic consortium that has received research funding from Abbott Nutrition, Nestle and Danone. No other disclosures were reported. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Padmapriya, Bernard, Tan, Chu, Goh, Tan, Shek, Chong, Tan, Chan, Yap, Godfrey, Lee, Meaney, Eriksson, Tan, Law and Müller-Riemenschneider.)

Background: Parental practices and neighbourhood environmental factors may influence children's movement behaviours. We aimed to investigate the cross-sectional and prospective associations of parental practices and neighbourhood environmental factors with accelerometer-measured 24-hour movement behaviours (24 h-MBs) among school-aged children in Singapore., Methods: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study collected information on dimensions of parental practices and neighbourhood environment at age 5.5 years. Confirmatory factor analyses were performed to generate latent variables and used to compute overall parental practices [involvement in PA + support for PA + control of screen viewing context] and environmental scores [facilities for active play + active mobility facilitators + barriers*-1]. Children wore an accelerometer on their non-dominant wrist for seven consecutive days at ages 5.5 and 8 years. The R-package GGIR 2.6 was used to derive moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), inactivity, and total-sleep (napping+night sleep) minutes per day. Associations were determined using compositional data analysis with multivariate linear regression models, taking into account potential confounders., Results: Among 425 children (48% girls, 59% Chinese), higher parental involvement in PA, parental support for PA and overall parental practices were associated with 24 h-MBs at ages 5.5 and 8 years, specifically with greater time spent in MVPA and less time being inactive relative to the remaining movement behaviours. The corresponding mean changes in the overall 24 h-MB for increasing parental practices from lowest to highest scores (- 2 to + 2 z-scores) indicated potential increases of up to 15-minutes in MVPA, 20-minutes in LPA, 5-minutes in sleep duration, and a reduction of 40-minutes in inactivity at age 5.5 years. At age 8 years, this could translate to approximately 15-minutes more of MVPA, 20-minutes more of LPA, a 20-minute reduction in sleep duration, and a 20-minute reduction in inactivity. Parental control of screen viewing contexts and neighbourhood environmental factors were not associated with 24 h-MBs., Conclusions: Parental practices but not environmental factors were associated with higher MVPA and lower inactivity among Singaporean children, even at a later age. Further research may provide insights that support development of targeted public health strategies to promote healthier movement behaviours among children., Study Registration: This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875., (© 2024. The Author(s).)

The sequence in the 5' untranslated regions (UTRs) is known to affect mRNA translation rates. However, the underlying regulatory grammar remains elusive. Here, we propose MTtrans, a multi-task translation rate predictor capable of learning common sequence patterns from datasets across various experimental techniques. The core premise is that common motifs are more likely to be genuinely involved in translation control. MTtrans outperforms existing methods in both accuracy and the ability to capture transferable motifs across species, highlighting its strength in identifying evolutionarily conserved sequence motifs. Our independent fluorescence-activated cell sorting coupled with deep sequencing (FACS-seq) experiment validates the impact of most motifs identified by MTtrans. Additionally, we introduce "GRU-rewiring," a technique to interpret the hidden states of the recurrent units. Gated recurrent unit (GRU)-rewiring allows us to identify regulatory element-enriched positions and examine the local effects of 5' UTR mutations. MTtrans is a powerful tool for deciphering the translation regulatory motifs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo -inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo -inositol as a preventive agent. However, the underlying molecular mechanisms by which myo -inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo -inositol in human parturition and explains possible underlying molecular mechanisms by which myo -inositol might modulate the uteroplacental environment and inhibit preterm labour onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour onset. A higher uteroplacental inositol level, potentially promoted by maternal myo -inositol supplementation, might affect lipid metabolism, eicosanoid production and secretion of pro-inflammatory chemocytokines that overall dampen the pro-labour uteroplacental environment responsible for labour onset and progress, thus reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo -inositol supplementation and definitively address the efficacy of myo -inositol prophylaxis against PTB.

Objective: Longitudinal changes in physical activity (PA) and sedentary behavior patterns from preconception to postpartum are not fully characterized. We examined changes and baseline sociodemographic/clinical correlates of PA and sedentary behavior in women from preconception to postpartum., Methods: The Singapore Preconception Study of Long-Term Maternal and Child Outcomes cohort recruited 1032 women planning pregnancy. Participants completed questionnaires at preconception, 34 to 36 weeks gestation, and 12 months postpartum. Repeated-measures linear regression models were used to analyze changes in walking, moderate to vigorous PA (MVPA), screen time, and total sedentary time, and to identify sociodemographic/clinical correlates associated with these changes., Results: Of the 373 women who delivered singleton live births, 281 provided questionnaires for all time points. Walking time increased from preconception to late pregnancy but decreased postpartum (adjusted means [95% CI]: 454 [333-575], 542 [433-651], and 434 [320-547] min/wk, respectively). Vigorous-intensity PA and MVPA decreased from preconception to late pregnancy but increased postpartum (vigorous-intensity PA: 44 [11-76], 1 [-3-5], and 11 [4-19] min/wk, MVPA: 273 [174-372], 165 [95-234], and 226 [126-325] min/wk, respectively). Screen time and total sedentary time remained consistent from preconception to pregnancy but decreased postpartum (screen: 238 [199-277], 244 [211-277], and 162 [136-189] min/d, total: 552 [506-598], 555 [514-596], and 454 [410-498] min/d, respectively). Individual characteristics of ethnicity, body mass index, employment, parity, and self-rated general health significantly influenced women's activity patterns., Conclusion: During late pregnancy, walking time increased, while MVPA declined significantly, and partially returned to preconception levels postpartum. Sedentary time remained stable during pregnancy but decreased postpartum. The identified set of sociodemographic/clinical correlates underscores need for targeted strategies.

Purpose : Variability in accelerometry-data processing decisions limited data comparability across studies. We aimed to examine different accelerometry-data processing rules: varying bout lengths and allowance of 0- and 2-min interruptions on the total and bout-accumulated time spent in moderate-to-vigorous physical activity (MVPA) and sedentary behavior estimates, and describe the distribution of activity time based on counts per min (CPM) in granular categories. Method : Using the Singapore Health 2 survey, this study included 746 adults (41.8% women, median age 45.0 years) who provided valid ActiGraph GT3X+ accelerometer-data (≥4 valid days with ≥10-h/day). Quantile regression analysis adjusting for accelerometry daily wear time, age, and gender was performed to calculate the median and interquartile range of accelerometry estimates. Results : Median MVPA time accumulated in bouts of 1-min versus bouts of 10-min was 39.2 min/day and 6.0 min/day, respectively. MVPA time was higher when considering a 2-min interruption (range: 1.8-39.2 min/day) compared to 0-min interruption (range: 0-35.5 min/day) across bout lengths of 1- to 15-min. Participants were sedentary (≤100 CPM) for a daily median of 7.6 h/day. Median activities min/day on the lower-intensity activity spectrum (100-2499 CPM) decreased from 63.4 to 4.6 min/day, while on the higher-intensity activity spectrum (≥2500 CPM) was ≤2.9 min/day. Men generally spent more time in MVPA than women. Conclusions : This study highlights the differences in accelerometry estimates based on data processing decisions, and the importance of quantifying accelerometry-based activity time across the granular intensity spectrum. More studies are warranted to understand the determinants and health impact of these behaviors.

Aims: To explore the glucose-overload hypothesis of artefactual gestational diabetes (GDM) diagnosis in shorter women during oral glucose tolerance testing (OGTT), by investigating associations between height and maternal glycemia; and GDM and pregnancy complications in height-groups., Methods: Women from GUSTO (n = 1100, 2009-2010) and NUH (n = 4068, 2017-2018) cohorts underwent a mid-gestation two and three time-point 75 g 2-hour OGTT, respectively. GDM-related complications (hypertensive disorders of pregnancy, preterm delivery, emergency cesarean section, neonatal intensive care unit admission, macrosomia, birthweight) were compared within shorter and taller groups, dichotomized by ethnic-specific median height., Results: Using WHO-1999 criteria, 18.8% (GUSTO) to 22.9% (NUH) of women were diagnosed with GDM-1999; and by WHO-2013 criteria, 21.9% (NUH) had GDM-2013. Each 5-cm height increment was inversely associated with GDM-1999 (adjusted odds ratio [aOR, 95% CI] = 0.81 [0.76-0.87], 2-h glycemia (adjusted β [aβ, 95% CI] = -0.171 mmol/L [-0.208, -0.135]) and 1-h glycemia (aβ = -0.160 mmol/L [-0.207, -0.112]). The inverse association between height and 2-h glycemia was most marked in "Other" ethnicities (Eurasians/Caucasians/mixed/other Asians) and Indians, followed by Chinese, then Malays. Compared with non-GDM, GDM-1999 was associated with preterm delivery (aOR = 1.76 [1.19-2.61]) and higher birthweight (aβ = 57.16 g [20.95, 93.38]) only among taller but not shorter women., Conclusions: Only taller women had an increased odds of GDM-related pregnancy complications. An artefactual GDM diagnosis due to glucose-overload among shorter women is plausible., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [KMG has received reimbursement for speaking at conferences sponsored by companies selling nutritional products. YSC, KMG and SYC are part of an academic consortium that has received research funding from Abbott Nutrition, Nestle and Danone. The other authors have no financial or personal conflict of interest to declare.], (Copyright © 2021 Elsevier B.V. All rights reserved.)

Context: Perturbed inositol physiology in insulin-resistant conditions has led to proposals of inositol supplementation for gestational diabetes (GDM) prevention, but placental inositol biology is poorly understood., Objective: Investigate associations of maternal glycemia with placental inositol content, determine glucose effects on placental expression of inositol enzymes and transporters, and examine relations with birthweight., Design and Participants: Case-control study of placentae from term singleton pregnancies (GDM n = 24, non-GDM n = 26), and culture of another 9 placentae in different concentrations of glucose and myo-inositol for 48 hours., Main Outcome Measures: Placental inositol was quantified by the Megazyme assay. Relative expression of enzymes involved in myo-inositol metabolism and plasma membrane inositol transport was determined by quantitative RT-PCR and immunoblotting. Linear regression analyses were adjusted for maternal age, body mass index, ethnicity, gestational age, and sex., Results: Placental inositol content was 17% lower in GDM compared with non-GDM. Higher maternal mid-gestation glycemia were associated with lower placental inositol. Increasing fasting glycemia was associated with lower protein levels of the myo-inositol synthesis enzyme, IMPA1, and the inositol transporters, SLC5A11 and SLC2A13, the expression of which also correlated with placental inositol content. In vitro, higher glucose concentrations reduced IMPA1 and SLC5A11 mRNA expression. Increasing fasting glycemia positively associated with customized birthweight percentile as expected in cases with low placental inositol, but this association was attenuated with high placental inositol., Conclusion: Glycemia-induced dysregulation of placental inositol synthesis and transport may be implicated in reduced placental inositol content in GDM, and this may in turn be permissive to accelerated fetal growth., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18-45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N = 557 censored). Women who successfully conceived (N = 475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N = 373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts. This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition, the S-PRESTO study draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

Background/objectives: Maternal glycaemia promotes fetal adiposity. Inositol, an insulin sensitizer, has been trialled for gestational diabetes prevention. The placenta has been implicated in how maternal hyperglycaemia generates fetal pathophysiology, but no studies have examined whether placental inositol biology is altered with maternal hyperglycaemia, nor whether such alterations impact fetal physiology. We aimed to investigate whether the effects of maternal glycaemia on offspring birthweight and adiposity at birth differed across placental inositol levels., Methods: Using longitudinal data from the Growing Up in Singapore Towards healthy Outcomes cohort, maternal fasting glucose (FPG) and 2-hour plasma glucose (2hPG) were obtained in pregnant women by a 75-g oral glucose tolerance test around 26 weeks' gestation. Relative placental inositol was quantified by liquid chromatography-mass spectrometry. Primary outcomes were birthweight (n = 884) and abdominal adipose tissue (AAT) volumes measured by neonatal MRI scanning in a subset (n = 262) of term singleton pregnancies. Multiple linear regression analyses were performed., Results: Placental inositol was lower in those with higher 2hPG, no exposure to tobacco smoke antenatally, with vaginal delivery and shorter gestation. Positive associations of FPG with birthweight (adjusted β [95% CI] 164.8 g [109.1, 220.5]) and AAT (17.3 ml [11.9, 22.6] per mmol glucose) were observed, with significant interactions between inositol tertiles and FPG in relation to these outcomes (p < 0.05). Stratification by inositol tertiles showed that each mmol/L increase in FPG was associated with increased birthweight and AAT volume among cases within the lowest (birthweight = 174.2 g [81.2, 267.2], AAT = 21.0 ml [13.1, 28.8]) and middle inositol tertiles (birthweight = 202.0 g [103.8, 300.1], AAT = 19.7 ml [9.7, 29.7]). However, no significant association was found among cases within the highest tertile (birthweight = 81.0 g [-21.2, 183.2], AAT = 0.8 ml [-8.4, 10.0])., Conclusions: High placental inositol may protect the fetus from the pro-adipogenic effects of maternal glycaemia. Studies are warranted to investigate whether prenatal inositol supplementation can increase placental inositol and reduce fetal adiposity.

Introduction: This study examined maternal, delivery and infant factors associated with cord thyroid-stimulating hormone (TSH) concentrations in an Asian population., Methods: The Growing Up in Singapore Towards healthy Outcomes (GUSTO) study is a mother-offspring birth cohort from 2 major hospitals in Singapore. Cord serum TSH was measured using the Abbott ARCHITECT TSH Chemiluminescent Microparticle Immunoassay and the ADVIA Centaur TSH-3 Immunoassay. After excluding infants with a maternal history of thyroid disease, screening cord TSH results from 604 infants were available for multivariable regression analysis in relation to the factors of interest., Results: Babies born by vaginal delivery had significantly higher cord serum TSH concentrations than babies born by caesarean section. Cord serum TSH concentrations differed significantly by measurement method. There was no association of cord TSH concentrations with ethnicity, sex, birth weight, gestational age, maternal body mass index, gestational weight gain, gestational diabetes mellitus status and other maternal, delivery and infant factors studied., Conclusion: Interpretation of cord serum TSH results may need to take into account mode of delivery and measurement method.

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 18-79 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 (≥8 h/night: β = 0.17,95% CI: 0.02-0.32; 7-< 8 h/night: β = 0.17,95% CI: 0.03-0.30 versus <6 h/night, p = 0.002), sleep quality (very good: β = 0.45,95% CI: 0.29-0.60; fairly good: β = 0.20,95% CI: 0.06-0.33 versus very/fairly bad; p trend < 0.001) and physical activity (high: β = 0.19,95% CI: 0.05-0.32; moderate: β = 0.15, 95% CI: 0.03-0.27 versus low; p trend < 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 'emotional support' and 'personal growth and autonomy'., 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.

We investigated whether adding anthropometric measures to HbA1c would have stronger discriminative ability over HbA1c alone in detecting dysglycemia (diabetes and prediabetes) among Asian women trying to conceive. Among 971 Singaporean women, multiple regression models and area under receiver-operating characteristic (AUROC) curves were used to analyze associations of anthropometric (weight, height, waist/hip circumferences, 4-site skinfold thicknesses) and HbA1c z-scores with dysglycemia (fasting glucose ≥6.1 mmol/L with 2-hour glucose ≥7.8 mmol/l). The prevalence of dysglycemia was 10.9%. After adjusting for sociodemographic/medical history, BMI (Odds Ratio [OR] = 1.62 [95%CI 1.32-1.99]), waist-to-height ratio (OR = 1.74 [1.39-2.17]) and total skinfolds (OR = 2.02 [1.60-2.55]) showed the strongest associations with dysglycemia but none outperformed HbA1c (OR = 4.09 [2.81-5.94]). After adjustment for history, adding BMI, waist-to-height ratio and total skinfolds (anthropometry trio) as continuous variables to HbA1c (AUROC = 0.80 [95%CI 0.75-0.85]) performed similarly to HbA1c alone (AUROC = 0.79 [0.74-0.84]). However, using clinically-defined thresholds without considering history, as in common clinical practice, BMI ≥ 23 kg/m 2  + HbA1c ≥ 5.7% (AUROC = 0.70 [0.64-0.75]) and anthropometry trio + HbA1c ≥ 5.7% (AUROC = 0.71 [0.65-0.76]) both outperformed HbA1c ≥ 5.7% alone (AUROC = 0.61 [0.57-0.65]). In a two-stage strategy, incorporating BMI ≥ 23 kg/m 2 alongside HbA1c ≥ 5.7% into first-stage screening to identify high risk women for subsequent oral glucose tolerance testing improves dysglycemia detection in Asian women preconception.

During normal pregnancy, increased insulin resistance acts as an adaptation to enhance materno-foetal nutrient transfer and meet the nutritional needs of the developing foetus, particularly in relation to glucose requirements. However, about 1 in 6 pregnancies worldwide is affected by the inability of the mother's metabolism to maintain normoglycaemia, with the combination of insulin resistance and insufficient insulin secretion resulting in gestational diabetes mellitus (GDM). A growing body of epidemiologic work demonstrates long-term implications for adverse offspring health resulting from exposure to GDM in utero. The effect of GDM on offspring obesity and cardiometabolic health may be partly influenced by maternal obesity; this suggests that improving glucose and weight control during early pregnancy, or better still before conception, has the potential to lessen the risk to the offspring. The consequences of GDM for microbiome modification in the offspring and the impact upon offspring immune dysregulation are actively developing research areas. Some studies have suggested that GDM impacts offspring neurodevelopmental and cognitive outcomes; confirmatory studies will need to separate the effect of GDM exposure from the complex interplay of social and environmental factors. Animal and human studies have demonstrated the role of epigenetic modifications in underpinning the predisposition to adverse health in offspring exposed to suboptimal hyperglycaemic in utero environment. To date, several epigenome-wide association studies in human have extended our knowledge on linking maternal diabetes-related DNA methylation marks with childhood adiposity-related outcomes. Identification of such epigenetic marks can help guide future research to develop candidate diagnostic biomarkers and preventive or therapeutic strategies. Longer-term interventions and longitudinal studies will be needed to better understand the causality, underlying mechanisms, or impact of GDM treatments to optimize the health of future generations., (© 2021 S. Karger AG, Basel.)

RNA-guided CRISPR-Cas9 proteins have been widely used for genome editing, but their off-target activities limit broad application. The minimal Cas9 ortholog from Staphylococcus aureus (SaCas9) is commonly used for in vivo genome editing; however, no variant conferring high genome-wide specificity is available. Here, we report rationally engineered SaCas9 variants with highly specific genome-wide activity in human cells without compromising on-target efficiency. One engineered variant, referred to as SaCas9-HF, dramatically improved genome-wide targeting accuracy based on the genome-wide unbiased identification of double-stranded breaks enabled by sequencing (GUIDE-seq) method and targeted deep sequencing analyses. Among 15 tested human endogenous sites with the canonical NNGRRT protospacer adjacent motif (PAM), SaCas9-HF rendered no detectable off-target activities at 9 sites, minimal off-target activities at 6 sites, and comparable on-target efficiencies to those of wild-type SaCas9. Furthermore, among 4 known promiscuous targeting sites, SaCas9-HF profoundly reduced off-target activities compared with wild type. When delivered by an adeno-associated virus vector, SaCas9-HF also showed reduced off-target effects when targeting VEGFA in a human retinal pigmented epithelium cell line compared with wild type. Then, we further altered a previously described variant named KKH-SaCas9 that has a wider PAM recognition range. Similarly, the resulting KKH-HF remarkably reduced off-target activities and increased on- to off-target editing ratios. Our finding provides an alternative to wild-type SaCas9 for genome editing applications requiring exceptional genome-wide precision., Competing Interests: The authors declare no competing interest.

Objectives: Examine the association between psychological variables and accelerometer-measured moderate-to-vigorous physical activity (MVPA) in urban Asians., Methods: A population-based cross-sectional study was conducted in Singapore. Participants wore an accelerometer for 7 days to measure physical activity (PA). Demographic, anthropometric and psychological data were also collected. Psychological variables included PA guideline knowledge, motivational profile for PA self-regulation (5 subscales), perceived barriers to PA (4 subscales) and perceived social support for PA. Regression models with adjustment for socio-demographic variables were fitted., Results: External regulation (b = - 13.03, 95% CI - 34.55; - 1.50) and perceived daily life barriers (b = - 12.63, 95% CI - 24.95; - 0.32) were significantly associated with fewer weekly MVPA minutes. A significant interaction between perceived social support and age (p = 0.046) was found. Social support was significantly negative associated with MVPA minutes in younger (< 28 years), but not in older participants., Conclusions: Considering levels of self-determination to engage in PA and perceived daily life barriers may be important for planning PA interventions in urban Asian populations. Caution is required when promoting social support for PA as it was associated with lower MVPA in younger people.

This study examined the validity and reliability of a domain-specific Adult Sedentary Behaviour Questionnaire (ASBQ) and the Global Physical Activity Questionnaire (GPAQ) single-item sitting question using self- and interviewer-administered modes of administration against the triaxial ActiGraph wGT3X-BT accelerometer. The ASBQ and the GPAQ were administered twice, seven days apart. Participants were asked to put on the waist-worn accelerometer for seven days. Convergent validity was assessed using Spearman's rho, mean absolute error (MAE), and Bland-Altman analysis ( n = 78). Reliability was assessed using the Spearman's rho and intraclass correlation coefficient (ICC) ( n = 84). Participants were adults aged 20-65 years and identifying as Chinese, Malay, or Indian. Only the self-administered GPAQ was significantly correlated with accelerometry-based measures (rho: 0.46), but not the interviewer-administered version (rho: 0.12). MAE for GPAQ was 207.5-218.3 min/day in relation to the accelerometer and for ASBQ was 154.7-174.6 min/day. Bland-Altman plots demonstrated large limits of agreement between questionnaire and accelerometry-based measures. While the self-administered GPAQ demonstrated a moderate correlation with accelerometry, the mean bias and the limits of agreement were large. The GPAQ (rho: 0.68-0.79; ICC: 0.68-0.78) and the ASBQ (rho: 0.53-0.64; ICC: 0.66-0.74) showed moderate-to-good reliability for total sedentary time using either self- or interviewer-administration. Future research should incorporate accelerometers to generate useful sedentary behaviour measures., Competing Interests: The authors declare no conflict of interest.

Background: The interpretation of previous studies on the association of physical activity and sedentary behaviour with psychological health is limited by the use of mostly self-reported physical activity and sedentary behaviour, and a focus on Western populations. We aimed to explore the association of self-reported and devise-based measures of physical activity and sedentary behaviour domains on psychological distress in an urban multi-ethnic Asian population., Methods: From a population-based cross-sectional study of adults aged 18-79 years, data were used from an overall sample (n = 2653) with complete self-reported total physical activity/sedentary behaviour and domain-specific physical activity data, and a subsample (n = 703) with self-reported domain-specific sedentary behaviour and accelerometry data. Physical activity and sedentary behaviour data were collected using the Global Physical Activity Questionnaire (GPAQ), a domain-specific sedentary behaviour questionnaire and accelerometers. The Kessler Screening Scale (K6) and General Health Questionnaire (GHQ-12) were used to assess psychological distress. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals, adjusted for socio-demographic and lifestyle characteristics., Results: The sample comprised 45.0% men (median age = 45.0 years). The prevalence of psychological distress based on the K6 and GHQ-12 was 8.4% and 21.7%, respectively. In the adjusted model, higher levels of self-reported moderate-to-vigorous physical activity (MVPA) were associated with significantly higher odds for K6 (OR = 1.47 [1.03-2.10]; p-trend = 0.03) but not GHQ-12 (OR = 0.97 [0.77-1.23]; p-trend = 0.79), when comparing the highest with the lowest tertile. Accelerometry-assessed MVPA was not significantly associated with K6 (p-trend = 0.50) nor GHQ-12 (p-trend = 0.74). The highest tertile of leisure-time physical activity, but not work- or transport-domain activity, was associated with less psychological distress using K6 (OR = 0.65 [0.43-0.97]; p-trend = 0.02) and GHQ-12 (OR = 0.72 [0.55-0.93]; p-trend = 0.01). Self-reported sedentary behaviour was not associated with K6 (p-trend = 0.90) and GHQ-12 (p-trend = 0.33). The highest tertile of accelerometry-assessed sedentary behaviour was associated with significantly higher odds for K6 (OR = 1.93 [1.00-3.75]; p-trend = 0.04), but not GHQ-12 (OR = 1.34 [0.86-2.08]; p-trend = 0.18)., Conclusions: Higher levels of leisure-time physical activity and lower levels of accelerometer-based sedentary behaviour were associated with lower psychological distress. This study underscores the importance of assessing accelerometer-based and domain-specific activity in relation to mental health, instead of solely focusing on total volume of activity.