Aim: To investigate the association between the experience of the coronavirus disease 2019 (COVID-19) pandemic and neurodevelopment of 6-month-old and 1-year-old children and explore the differences in the association by birth order.Methods: This comparison study was embedded in the Born in Guangzhou Cohort Study in China. The exposed group included 546 6-month-old and 285 1-year-old children who attended neurodevelopment assessments between March 1 and May 15, 2020, and the non-exposed group included 3,009 6-month-old and 2,214 1-year-old children during the same months from 2015 to 2019. Neurodevelopment at age 6 months and 1 year was assessed by trained clinical staff using the Ages and Stages Questionnaires, third edition (ASQ-3) and the Gesell Developmental Schedules (GDS).Results: The experience of the pandemic in 2020 was associated with a higher risk of delay in the fine motor (adjusted OR: 2.50, 95% CI: 1.25, 4.99; estimated by logistic regression) and communication (adjusted RR [aRR]: 1.13, 95% CI: 1.02, 1.25; estimated by log-binomial regression) domains at age 1 year. The association between the experience of the pandemic and communication delay at age 1 year only existed in first-born children (aRR: 1.15, 95% CI: 1.03, 1.30) but not in later-born children (aRR: 1.02, 95% CI: 0.84, 1.25). No associations were observed in any domain among 6-month-olds.Conclusion: Experiencing the COVID-19 pandemic and related public health strategies might be associated with a higher risk of delay in the development of fine motor and communication in 1-year-old children; the association observed in the communication domain only existed in first-born children.

Aims/hypothesis Metformin use has been associated with reduced incidence of dementia in diabetic individuals in observational studies. However, the causality between the two in the general population is unclear. This study uses Mendelian randomisation (MR) to investigate the causal effect of metformin targets on Alzheimer’s disease and potential causal mechanisms in the brain linking the two. Methods Genetic proxies for the effects of metformin drug targets were identified as variants in the gene for the corresponding target that associated with HbA1c level (N=344,182) and expression level of the corresponding gene (N≤31,684). The cognitive outcomes were derived from genome-wide association studies comprising 527,138 middle-aged Europeans, including 71,880 with Alzheimer’s disease or Alzheimer’s disease-by-proxy. MR estimates representing lifelong metformin use on Alzheimer’s disease and cognitive function in the general population were generated. Effect of expression level of 22 metformin-related genes in brain cortex (N=6601 donors) on Alzheimer’s disease was further estimated. Results Genetically proxied metformin use, equivalent to a 6.75 mmol/mol (1.09%) reduction on HbA1c, was associated with 4% lower odds of Alzheimer’s disease (OR 0.96 [95% CI 0.95, 0.98], p=1.06×10−4) in non-diabetic individuals. One metformin target, mitochondrial complex 1 (MCI), showed a robust effect on Alzheimer’s disease (OR 0.88, p=4.73×10−4) that was independent of AMP-activated protein kinase. MR of expression in brain cortex tissue showed that decreased MCI-related gene (NDUFA2) expression was associated with lower Alzheimer’s disease risk (OR 0.95, p=4.64×10−4) and favourable cognitive function. Conclusions/interpretation Metformin use may cause reduced Alzheimer’s disease risk in the general population. Mitochondrial function and the NDUFA2 gene are plausible mechanisms of action in dementia protection. Graphical abstract

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Abnormal m6A methylation plays a significant role in cancer progression. Increasingly, researchers have focused on developing lncRNA signatures to evaluate the prognosis of cancer patients. The specific function of m6A-related lncRNAs in the prognosis of bladder cancer patients and the immune microenvironment of bladder cancer remains elusive. Herein, we performed a comprehensive analysis of m6A-related lncRNA prognostic values and their association with the immune microenvironment in bladder cancer using the TCGA dataset. A total of 9 m6A-related lncRNAs were dramatically correlated with overall survival outcomes in bladder cancer. Two molecular subtypes (cluster 1 and cluster 2) were identified by consensus clustering for 9 m6A-related prognostic lncRNAs. Cluster 1 was significantly correlated with poor prognosis, advanced clinical stage, higher PD-L1 expression, a higher ESTIMATEScore and immuneScore, and distinct immune cell infiltration. GSEA revealed the enrichment of apoptosis and the JAK-STAT signaling pathway in cluster 2. A prognostic risk score was constructed using 9 m6A-related prognostic lncRNAs, which functioned as an independent prognostic factor for bladder cancer. Moreover, bladder cancer patients in the low-risk score group had a higher pN stage, pT stage, and clinical stage and a lower tumor grade and immuneScore. The risk score was correlated with the infiltration levels of certain immune cells, including B cells, plasma cells, follicular helper T cells, regulatory T cells, resting NK cells, neutrophils, M0 macrophages, M1 macrophages, and M2 macrophages. Collectively, our study elucidated the important role of m6A-related lncRNAs in the prognosis of bladder cancer patients and in the bladder cancer immune microenvironment. The results suggest that the components of the m6A-related prognostic lncRNA signature might serve as a crucial mediator of the immune microenvironment in bladder cancer, representing promising therapeutic targets for improving immunotherapeutic efficacy.

BackgroundEvidence on the relationship between fruit and vegetable consumption (FV) and mental health in adolescence is sparse and inconsistent. Social determinants of FV include ethnicity, family environments and economic disadvantage. We investigated the relationship between FV and mental health in the British multi-ethnic Determinants of Adolescents (now young Adult) Social well-being and Health (DASH) longitudinal study.MethodsA longitudinal study of 4683 adolescents living in London at age 11–13 years and followed up at 14–16 years. FV was measured using validated questions on the number of portions consumed daily. Mental health was measured by the Strengths and Difficulties Questionnaire as mean Total Difficulties Score (TDS) and by classification as a ‘probable clinical case’ (TDS > 17). Social measures included ethnicity, parenting and socioeconomic circumstances. Multilevel modelling was used to investigate the association between FV and mental health throughout adolescence.ResultsLow FV was common among adolescents, with approximately 60–70% of adolescents reporting < 5 portions/day and 20–30% reporting < 1 portion/day. In late adolescence, most ethnic minority groups reported lower FV than their White peers. In fully adjusted models, < 1 portion/day remained a significant correlate with mean TDS (Coef: 0.55, 0.29–0.81, P < 0.001) and TDS > 17 (Odds Ratio: 1.43, 1.11–1.85, P = 0.007). Gender- or ethnic-specific effects were not observed. Low parental care partly attenuated the association between FV and mental health.ConclusionsLow FV is a longitudinal correlate of poor mental health across adolescence. A focus on FV in parenting interventions could yield interrelated benefits across developmental outcomes given its importance to both physical and socioemotional health.Electronic supplementary materialThe online version of this article (10.1186/s12966-019-0780-y) contains supplementary material, which is available to authorized users.