Shirong Cai

Lactobacillus rhamnosus GG induces tumor regression in mice bearing orthotopic bladder tumors

(Cancer Sci 2010; 101: 751–758)

Infant feeding effects on early neurocognitive development in Asian children

BACKGROUND Breastfeeding has been shown to enhance global measures of intelligence in children. However, few studies have examined associations between breastfeeding and specific cognitive task performance in the first 2 y of life, particularly in an Asian population. OBJECTIVE We assessed associations between early infant feeding and detailed measures of cognitive development in the first 2 y of life in healthy Asian children born at term. DESIGN In a prospective cohort study, neurocognitive testing was performed in 408 healthy children (aged 6, 18, and 24 mo) from uncomplicated pregnancies (i.e., birth weight >2500 and <4000 g, gestational age ≥37 wk, and 5-min Apgar score ≥9). Tests included memory (deferred imitation, relational binding, habituation) and attention tasks (visual expectation, auditory oddball) as well as the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Children were stratified into 3 groups (low, intermediate, and high) on the basis of breastfeeding duration and exclusivity. RESULTS After potential confounding variables were controlled for, significant associations and dose-response relations were observed for 4 of the 15 tests. Higher breastfeeding exposure was associated with better memory at 6 mo, demonstrated by greater preferential looking toward correctly matched items during early portions of a relational memory task (i.e., relational binding task: P-trend = 0.015 and 0.050 for the first two 1000-ms time bins, respectively). No effects of breastfeeding were observed at 18 mo. At 24 mo, breastfed children were more likely to display sequential memory during a deferred imitation memory task (P-trend = 0.048), and toddlers with more exposure to breastfeeding scored higher in receptive language [+0.93 (0.23, 1.63) and +1.08 (0.10, 2.07) for intermediate- and high-breastfeeding groups, respectively, compared with the low-breastfeeding group], as well as expressive language [+0.58 (-0.06, 1.23) and +1.22 (0.32, 2.12) for intermediate- and high-breastfeeding groups, respectively] assessed via the BSID-III. CONCLUSIONS Our findings suggest small but significant benefits of breastfeeding for some aspects of memory and language development in the first 2 y of life, with significant improvements in only 4 of 15 indicators. Whether the implicated processes confer developmental advantages is unknown and represents an important area for future research. This trial was registered at www.clinicaltrials.gov as NCT01174875.

Sleep Quality and Nocturnal Sleep Duration in Pregnancy and Risk of Gestational Diabetes Mellitus

Study Objectives: To examine the influence of maternal sleep quality and nocturnal sleep duration on risk of gestational diabetes mellitus (GDM) in a multiethnic Asian population. Methods: A cohort of 686 women (376 Chinese, 186 Malay, and 124 Indian) with a singleton pregnancy attended a clinic visit at 26‐28 weeks of gestation as part of the Growing Up in Singapore Towards healthy Outcomes mother‐offspring cohort study. Self‐reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index (PSQI). GDM was diagnosed based on a 75‐g oral glucose tolerance test administered after an overnight fast (1999 WHO criteria). Multiple logistic regression was used to model separately the associations of poor sleep quality (PSQI score > 5) and short nocturnal sleep duration (<6 h) with GDM, adjusting for age, ethnicity, maternal education, body mass index, previous history of GDM, and anxiety (State‐Trait Anxiety Inventory score). Results: In the cohort 296 women (43.1%) had poor sleep quality and 77 women (11.2%) were categorized as short sleepers; 131 women (19.1%) were diagnosed with GDM. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of GDM (poor sleep, adjusted odds ratio [OR] = 1.75, 95% confidence interval [CI] 1.11 to 2.76; short sleep, adjusted OR = 1.96, 95% CI 1.05 to 3.66). Conclusions: During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibited abnormal glucose regulation. Treating sleep problems and improving sleep behavior in pregnancy could potentially reduce the risk and burden of GDM.

Live and lyophilized Lactobacillus species elicit differential immunomodulatory effects on immune cells

To study the mechanism of action of the lactobacilli, splenocytes were incubated with lactobacilli. We compared the ability of live and lyophilized Lactobacillus casei, Lactobacillus rhamnosus GG and Lactobacillus delbrueckii ssp. bulgaricus to modulate the production of interleukin 12p40 (IL-12p40), tumor necrosis factor alpha and IL-10 by splenocytes from C57BL/6 and BALB/c mice. Blocking contact between lactobacilli and immune cells abrogated all cytokine production. Toll-like receptor 2 (TLR2) was partially responsible, but not TLR4 or TLR9, for the induction of cytokine production in splenocytes. All cytokine production declined to basal levels when bacterial phagocytosis was inhibited. This shows that lactobacilli stimulation of cytokine production in splenocytes requires the process of phagocytosis and engagement of TLR2, but not TLR4 or TLR9.

Sleep duration and growth outcomes across the first two years of life in the GUSTO study

BACKGROUND AND AIM Short sleep duration is thought to be a factor contributing to increased body mass index (BMI) in both school-age children and adults. Our aim was to determine whether sleep duration associates with growth outcomes during the first two years of life. STUDY DESIGN Participants included 899 children enrolled in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) birth cohort study. Anthropometric data (weight and body length) and parental reports of sleep duration were collected at 3, 6, 9, 12, 18, and 24 months of age. A mixed-model analysis was used to evaluate the longitudinal association of BMI and body length with sleep duration. In subgroup analyses, effects of ethnicity (Chinese, Indian, and Malay) and short sleep at three months of age (≤12 h per day) were examined on subsequent growth measures. RESULTS In the overall cohort, sleep duration was significantly associated with body length (β = 0.028, 95% confidence interval [CI] 0.002-0.053, p = 0.033), but not BMI, after adjustment for potential confounding factors. Only in Malay children, shorter sleep was associated with a higher BMI (β = -0.042, 95% CI -0.071 to -0.012, p = 0.005) and shorter body length (β = 0.079, 95% CI 0.030-0.128, p = 0.002). In addition, shorter sleep was associated with a higher BMI and shorter body length in children who slept ≤12 h per day at three months of age. CONCLUSION The association between sleep duration and growth outcomes begins in infancy. The small but significant relationship between sleep and growth anthropometric measures in early life might be amplified in later childhood.

Eye size and shape in newborn children and their relation to axial length and refraction at 3 years

To determine if eye size and shape at birth are associated with eye size and refractive error 3 years later.

Lactobacillus rhamnosus GG Activation of Dendritic Cells and Neutrophils Depends on the Dose and Time of Exposure

This study evaluates the ability of Lactobacillus rhamnosus GG (LGG) to activate DC and neutrophils and modulate T cell activation and the impact of bacterial dose on these responses. Murine bone marrow derived DC or neutrophils were stimulated with LGG at ratios of 5 : 1, 10 : 1, and 100 : 1 (LGG : cells) and DC maturation (CD40, CD80, CD86, CD83, and MHC class II) and cytokine production (IL-10, TNF-α, and IL-12p70) were examined after 2 h and 18 h coculture and compared to the ability of BCG (the present immunotherapeutic agent for bladder cancer) to stimulate these cells. A 2 h exposure to 100 : 1 (high dose) or an 18 h exposure to 5 : 1 or 10 : 1 (low dose), LGG : cells, induced the highest production of IL-12 and upregulation of CD40, CD80, CD86, and MHC II on DC. In DCs stimulated with LGG activated neutrophils IL-12 production decreased with increasing dose. LGG induced 10-fold greater IL-12 production than BCG. T cell IFNγ and IL-2 production was significantly greater when stimulated with DC activated with low dose LGG. In conclusion, DC or DC activated with neutrophils exposed to low dose LGG induced greater Th1 polarization in T cells and this could potentially exert stronger antitumor effects. Thus the dose of LGG used for immunotherapy could determine treatment efficacy.

Higher Maternal Dietary Protein Intake Is Associated with a Higher Risk of Gestational Diabetes Mellitus in a Multiethnic Asian Cohort

Background: Dietary protein may affect glucose metabolism through several mechanisms, but results from studies on dietary protein intake and risk of gestational diabetes mellitus (GDM) have been inconsistent.Objective: We examined the cross-sectional associations of dietary protein intake from different food sources during pregnancy with the risk of GDM in a multiethnic Asian population.Methods: We included 980 participants with singleton pregnancies from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort. Protein intake was ascertained from 24-h dietary recall and 3-d food diaries at 26-28 wk gestation. GDM was defined as fasting glucose ≥7.0 mmol/L and/or 2-h postload glucose ≥7.8 mmol/L at 26-28 wk gestation. We evaluated the association of dietary protein intake with GDM risk by substituting carbohydrate with protein in an isocaloric model with the use of multivariable logistic regression analysis.Results: The prevalence of GDM was 17.9% among our participants. After adjustment for potential confounders, a higher total dietary protein intake was associated with a higher risk of GDM; the OR comparing the highest with the lowest quartile of intake was 2.15 (95% CI: 1.27, 3.62; P-trend = 0.016). Higher intake levels of both animal protein (OR: 2.87; 95% CI: 1.58, 5.20; P-trend = 0.001) and vegetable protein (OR: 1.78; 95% CI: 0.99, 3.20; P-trend = 0.009) were associated with a higher risk of GDM. Among the animal protein sources, higher intake levels of seafood protein (OR: 2.17; 95% CI: 1.26, 3.72; P-trend = 0.023) and dairy protein (OR: 1.87; 95% CI: 1.11, 3.15; P-trend = 0.017) were significantly associated with a higher GDM risk.Conclusion: Higher intake levels of both animal and vegetable protein were associated with a higher risk of GDM in Asian women. This trial was registered at clinicaltrials.gov as NCT01174875.

Axial Length/Corneal Radius of Curvature Ratio and Myopia in 3-Year-Old Children.

Purpose This study investigated the association of axial length (AL) to corneal radius of curvature (CRC) ratio with spherical equivalent (SE) in a 3-year old Asian cohort. Methods Three-hundred forty-nine 3-year old Asian children from The Growing Up in Singapore towards Healthy Outcomes (GUSTO) birth cohort study underwent AL and CRC measurements with a noncontact ocular biometer and cycloplegic refraction using an autorefractor. The ratio of AL to CRC (AL/CRC) was calculated for all the participants, and subsequently AL, CRC, and AL/CRC were analyzed in relationship to SE. Results The SE showed better correlation with AL/CRC (Spearmans correlation coefficient, ρ = −0.53; 95% confidence interval [CI]: −0.66; −0.49; P < 0.001) compared to either AL or CRC alone ([ρ = −0.36; 95% CI: −0.51 to 0.51; P = 0.01] and [ρ = 0.05; 95% CI: −0.04 to 0.17; P = 0.34], respectively). Mean AL/CRC was 2.91 ± 0.06 among myopes and decreased to 2.79 ± 0.06 among hyperopes. Axial length to corneal radius of curvature was strongly correlated with SE in myopes (ρ = −0.78; 95% CI: −3.76; −0.79; P = < 0.001), but not in emmetropes and hyperopes ([ρ = −0.39; 95% CI: −10.73; −0.57; P = 0.01] and [ρ = −0.18; 95% CI: −17.28; 12.42; P = 0.38], respectively). Linear regression adjusted for gender and ethnicity showed a 0.74-diopter shift in SE towards myopia with every 0.1 increase in AL/CRC ratio (P < 0.001, r2 = 0.33). Conclusion The correlation between SE and AL/CRC is stronger than that between AL or CRC alone. This suggests that in a research setting, when cycloplegic refraction is difficult to perform on 3-year-old children, AL/CRC may be the next best reference for refractive error. Translational Relevance In the research setting, AL/CRC may be the next best reference for refractive error over AL alone when cycloplegic refraction is unavailable in 3-year old children.

Maternal hyperglycemia in singleton pregnancies conceived by IVF may be modified by first-trimester BMI

Abstract STUDY QUESTION Does IVF independently increase the risk of gestational diabetes mellitus (GDM) and is this increase in risk modified by maternal body mass index? SUMMARY ANSWER IVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women (BMI > 25 kg/m2). WHAT IS KNOWN ALREADY IVF has been associated with increased risk of GDM, but most previous studies did not adequately assess confounding or effect modification by other risk factors. STUDY DESIGN, SIZE, DURATION Cross-sectional study using data from 1089 women with singleton pregnancies who participated in a Singaporean birth cohort study (GUSTO) and received a 75 g oral glucose tolerance test (OGTT) at 26–28 weeks gestation. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 1089 women (n = 1013 conceived spontaneously, n = 76 conceived through IVF) with singleton pregnancies received a 75 g OGTT at 26–28 weeks gestation. Fasting and 2 h postprandial blood glucose levels were assayed. World Health Organization criteria (1999) standard criteria were used to classify GDM: ≥7.0 mmol/L for fasting and/or ≥7.8 mmol/L for 2-h postprandial plasma glucose levels, which was the clinical guideline in use during the study. MAIN RESULTS AND THE ROLE OF CHANCE IVF pregnancies had nearly double the odds of GDM (OR = 1.83, 95% CI: 1.03–3.26) and elevated fasting (mean difference = 0.12 mmol/L, 95% CI: 0.00–0.24) and OGTT 2-h blood glucose levels (mean difference = 0.64 mmol/L, 95% CI: 0.27–1.01), after adjusting for commonly recognized risk factors for GDM. After stratification by first-trimester BMI, these increased risks of GDM (OR = 3.54, 95% CI: 1.44–8.72) and elevated fasting (mean difference = 0.39 mmol/L, 95% CI: 0.13–0.65) and 2-h blood (mean difference = 1.24 mmol/L, 95% CI: 0.56–1.91) glucose levels were significant only in the IVF group who is also overweight or obese (BMI > 25 kg/m2). LIMITATIONS REASONS FOR CAUTION One limitation of our study is the absence of a 1 h post-OGTT plasma glucose sample, as we were using the 1999 WHO diagnostic criteria (the clinical guideline in Singapore) at the time of our study, instead of the revised 2013 WHO diagnostic criteria. Our cohort may not be representative of the general Singapore obstetric population, although participants were recruited from the two largest maternity hospitals in the country and include both private and subsidized patients. WIDER IMPLICATIONS OF THE FINDINGS IVF appears to be an independent risk factor for GDM and elevated blood glucose levels in overweight women. Our findings reinforce the need to advise overweight or obese women contemplating IVF to lose weight before the procedure to reduce their risk of GDM and hyperglycemia-related adverse outcomes arising therefrom. In settings where universal GDM screening is not routine, overweight or obese women who conceive by IVF should be screened. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Program and administered by the Singapore Ministry of Healths National Medical Research Council (NMRC), Singapore (NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014). Additional funding was provided by the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR). K.M.G. and Y.S.C. have received lecture fees from Nestle Nutrition Institute and Danone, respectively. K.M.G., Y.S.C. and S.Y.C. are part of an academic consortium that has received research funding from Abbott Nutrition, Nestec and Danone. The other authors have nothing to disclose. The other authors have nothing to disclose. TRIAL REGISTRATION NUMBER N/A.