Background: Although prior studies showed a correlation between environmental manganese (Mn) exposure and neurodevelopmental disorders in children, the results have been inconclusive. There has yet been no consistent biomarker of environmental Mn exposure. Here, we summarized studies that investigated associations between manganese in biomarkers and childhood neurodevelopment and suggest a reliable biomarker.Methods: We searched PubMed and Web of Science for potentially relevant articles published until December 31th 2019 in English. We also conducted a meta-analysis to quantify the effects of manganese exposure on Intelligence Quotient (IQ) and the correlations of manganese in different indicators.Results: Of 1754 citations identified, 55 studies with 13,388 subjects were included. Evidence from cohort studies found that higher manganese exposure had a negative effect on neurodevelopment, mostly influencing cognitive and motor skills in children under 6 years of age, as indicated by various metrics. Results from cross-sectional studies revealed that elevated Mn in hair (H-Mn) and drinking water (W-Mn), but not blood (B-Mn) or teeth (T-Mn), were associated with poorer cognitive and behavioral performance in children aged 6–18 years old. Of these cross-sectional studies, most papers reported that the mean of H-Mn was more than 0.55 μg/g. The meta-analysis concerning H-Mn suggested that a 10-fold increase in hair manganese was associated with a decrease of 2.51 points (95% confidence interval (CI), − 4.58, − 0.45) in Full Scale IQ, while the meta-analysis of B-Mn and W-Mn generated no such significant effects. The pooled correlation analysis revealed that H-Mn showed a more consistent correlation with W-Mn than B-Mn. Results regarding sex differences of manganese associations were inconsistent, although the preliminary meta-analysis found that higher W-Mn was associated with better Performance IQ only in boys, at a relatively low water manganese concentrations (most below 50 μg/L).Conclusions: Higher manganese exposure is adversely associated with childhood neurodevelopment. Hair is the most reliable indicator of manganese exposure for children at 6–18 years of age. Analysis of the publications demonstrated sex differences in neurodevelopment upon manganese exposure, although a clear pattern has not yet been elucidated for this facet of our study.

Several B vitamins are essential in the one-carbon metabolism pathway, which is central to DNA methylation, synthesis, and repair. Moreover, an imbalance in this pathway has been linked to certain types of cancers. Here, we performed a meta-analysis in order to investigate the relationship between the intake of four dietary one-carbon metabolism-related B vitamins (B2, B6, folate, and B12) and the risk of esophageal cancer (EC). We searched PubMed, Web of Science, and Embase for relevant studies published through 1 March 2018. The odds ratio (OR) with 95% confidence interval (CI) for the highest versus the lowest level of each dietary B vitamin was then calculated. From 21 articles reporting 26 studies including 6404 EC cases and 504,550 controls, we found an inverse correlation between the consumption of vitamin B6 and folate and the risk of EC; this association was specific to the US, Europe, and Australia, but was not found in Asia. A dose-response analysis revealed that each 100 μg/day increase in folate intake reduced the risk of EC by 12%. Moreover, each 1 mg/day increase in vitamin B6 intake decreased the risk of EC by 16%. Surprisingly, we found that each 1 μg/day increase in vitamin B12 intake increased the risk of esophageal adenocarcinoma by 2%, particularly in the US and Europe, suggesting both geographic and histological differences. Together, our results suggest that an increased intake of one-carbon metabolism-related B vitamins may protect against EC, with the exception of vitamin B12, which should be consumed in moderation.

Although several epidemiological studies have investigated the association between dietary calcium intake and the risk of esophageal cancer, the results are inconsistent. This study aimed to make a comprehensive evaluation regarding the association between calcium intake and risk of esophageal cancer through a meta-analysis approach. We searched for all relevant articles from the inception to April 2017, using PUBMED, EMBASE, and Web of Knowledge. The pooled odds ratio (ORs) with the 95% confidence interval (95% CI) for the highest versus the lowest categories of calcium intake was calculated using a Mantel–Haenszel fixed-effect model. In total, 15 articles reporting 17 studies including 3396 esophageal cancer cases and 346,815 controls were selected for the meta-analysis. By comparing the highest vs. the lowest levels of dietary calcium intake, we found that dietary calcium intake was inversely associated with the risk of esophageal cancer (OR = 0.80, 95% CI: 0.71–0.91, I² = 33.6%). The subgroup analysis indicated that the protective function of dietary calcium intake were observed in esophageal squamous cell cancer, but not in esophageal adenocarcinoma in the studies conducted in Asia, but not those in Europe and America. In conclusion, our results suggest that higher dietary calcium intake is associated with a lower risk of esophageal cancer—especially esophageal squamous cell cancer—in Asian populations, though more data from prospective cohort studies are needed.

Objectives The association between visceral adiposity index (VAI) and the prevalence of non-alcoholic fatty liver disease (NAFLD) has not been fully determined. Here, we aimed to explore the association between VAI and NAFLD in the general US population, and further investigate whether the association involves population differences. Design Cross-sectional population-based study. Setting The National Health and Nutrition Examination Survey (2003–2018). Participants A total of 7522 participants aged 20 years or older who have complete information for NAFLD assessment test were included in this study. Primary and secondary outcome measures NAFLD was assessed by the modified fatty liver index for the US population (USFLI) using a cut-off point of 30. Correlation between VAI and NAFLD prediction scores was calculated using the partial correlation analysis. Logistic regression models were further used to estimate ORs and 95% CIs. Results Insulin resistance (IR), inflammation and waist circumference-adjusted partial correlation analysis indicated that VAI scores were positively correlated with USFLI (r=0.404 for men, and r=0.395 for women; p<0.001). In a comparison of the highest versus the lowest quartiles of VAI, multivariable logistic regression analysis demonstrated a positive association between VAI and NAFLD (OR (95% CI)=1.97 (1.12 to 3.47) for men, OR (95% CI)=4.03 (1.98 to 8.20) for women). The stratified analyses revealed that the positive association involves age/gender-specific and ethnic differences. As for the impact of metabolic disorders, our results revealed that the association was independent of IR and diabetes, but it would be confounded by other metabolic disorders. However, no significant association was found between VAI and hepatic fibrosis. Conclusion VAI is positively associated with the prevalence of NAFLD, but not hepatic fibrosis among US adults, and the association involves age/gender-specific and ethnic differences. The results reported here have important public health implications in NAFLD screening in the future.