Associations of risk factor burden and genetic predisposition with the 10-year risk of atrial fibrillation: observations from a large prospective study of 348,904 participants

BackgroundUnderstanding the effects of risk factor burden and genetic predisposition on the long-term risk of atrial fibrillation (AF) is important to improve public health initiatives. However, the 10-year risk of AF considering risk factor burden and genetic predisposition is unknown.MethodsA total of 348,904 genetically unrelated participants without AF at baseline from the UK were categorized into three groups: index ages 45 years (n = 84,206), 55 years (n=117,520), and 65 years (n=147,178). Optimal, borderline, or elevated risk factor burden was determined by body mass index, blood pressure, diabetes mellitus, alcohol consumption, smoking status, and history of myocardial infarction or heart failure. Genetic predisposition was estimated using the polygenic risk score (PRS), constructed using 165 predefined genetic risk variants. The combined effects of risk factor burden and PRS on the risk of incident AF in 10 years were estimated for each index age. Fine and Gray models were developed to predict the 10-year risk of AF.ResultsThe overall 10-year risk of AF was 0.67% (95% CI: 0.61-0.73%) for index age 45 years, 2.05% (95% CI: 1.96-2.13%) for index age 55 years, and 6.34% (95% CI: 6.21-6.46%) for index age 65 years, respectively. An optimal risk factor burden was associated with later AF onset regardless of genetic predisposition and sex (P ConclusionsRisk factor burden together with a genetic predisposition is associated with the 10-year risk of AF. Our results may be helpful in selecting high-risk individuals for primary prevention of AF and facilitating subsequent health interventions

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Exposure Profile and Characteristics of Parabens and Alkylphenols in Plasma among Rural Adults in Central China

Parabens and alkylphenols pose serious hazards to human health, yet there are few studies on their exposure profiles and health risks in rural Chinese populations. In this study, 804 participants were selected from the Henan Rural Cohort in mid-eastern China. The plasma levels of parabens (methylparaben, ethylparaben, propylparaben, butylparaben (BuP)) and alkylphenols (4-tert-butylphenol (4-t-BP), 4-tert-octylphenol (4-t-OP)) were analyzed via liquid chromatography–tandem mass spectrometry. Linear regression models were used to investigate factors that may influence pollutant exposure levels. The correlation between contaminants was assessed using Spearman’s correlation. The human contaminant intake was estimated using the estimated daily intake (EDI). The health risk was assessed using the hazard quotient (HQ). The detection frequency of four parabens and two alkylphenols exceeded 75%, with median concentrations of 0.444, 0.067, 0.078, 0.053, 8.810, and 6.401 ng/mL, respectively. Significant correlations were observed between parabens, as well as between 4-t-BP and 4-t-OP. Regarding gender, paraben concentrations were higher in women than in men, except for BuP. The EDI for pollutants except 4-t-OP was lower than their respective tolerable/acceptable daily intake. In total, 85.70% of participants had 4-t-OP HQ > 1. A widespread exposure to parabens and alkylphenols among the rural population was found. The high health risks of alkylphenol exposure indicate that alkylphenols should be used with caution

Gradient matters via filament diameter-adjustable 3D printing

Abstract Gradient matters with hierarchical structures endow the natural world with excellent integrity and diversity. Currently, direct ink writing 3D printing is attracting tremendous interest, and has been used to explore the fabrication of 1D and 2D hierarchical structures by adjusting the diameter, spacing, and angle between filaments. However, it is difficult to generate complex 3D gradient matters owing to the inherent limitations of existing methods in terms of available gradient dimension, gradient resolution, and shape fidelity. Here, we report a filament diameter-adjustable 3D printing strategy that enables conventional extrusion 3D printers to produce 1D, 2D, and 3D gradient matters with tunable heterogeneous structures by continuously varying the volume of deposited ink on the printing trajectory. In detail, we develop diameter-programmable filaments by customizing the printing velocity and height. To achieve high shape fidelity, we specially add supporting layers at needed locations. Finally, we showcase multi-disciplinary applications of our strategy in creating horizontal, radial, and axial gradient structures, letter-embedded structures, metastructures, tissue-mimicking scaffolds, flexible electronics, and time-driven devices. By showing the potential of this strategy, we anticipate that it could be easily extended to a variety of filament-based additive manufacturing technologies and facilitate the development of functionally graded structures

Association of Canonical Wnt/β-Catenin Pathway and Type 2 Diabetes: Genetic Epidemiological Study in Han Chinese

We aimed to investigate the associations of polymorphisms in Canonical Wnt/β-catenin pathway (WNT) signaling genes (including low-density lipoprotein-related protein 5 [LRP5] and transcription factor 7-like 2 [TCF7L2] gene) and the downstream gene glucagon (GCG) and risk of type 2 diabetes mellitus (T2DM) in a Han Chinese population. We genotyped the single nucleotide polymorphisms (SNPs) for LRP5, TCF7L2 and GCG gene were genotyped in 1842 patients with T2DM and 7777 normal glucose-tolerant healthy subjects. We used multifactor dimensionality reduction (MDR) and multiplicative logistic regression adjusting for sex, age, anthropometric measurements and lipid levels to investigate the gene-gene interactions for the risk of T2DM. Among the five SNPs in LRP5, the recessive model of rs7102273 and the haplotype GCTCC were associated with T2DM risk; the haplotype GCTTC was associated with decreased risk. For TCF7L2, the rs11196218 genotype GA and the haplotype CCG, TTG, TTA were associated with T2DM risk; whereas, the haplotype CTG and TCG were associated with decreased risk. Both MDR and multiplicative logistic regression revealed potential gene–gene interactions among LRP5, TCF7L2, and GCG associated with T2DM. The WNT signaling pathway may play a significant role in risk of T2DM in Han Chinese people

Fractal Design Boosts Extrusion-Based 3D Printing of Bone-Mimicking Radial-Gradient Scaffolds

Although extrusion-based three-dimensional (EB-3D) printing technique has been widely used in the complex fabrication of bone tissue-engineered scaffolds, a natural bone-like radial-gradient scaffold by this processing method is of huge challenge and still unmet. Inspired by a typical fractal structure of Koch snowflake, for the first time, a fractal-like porous scaffold with a controllable hierarchical gradient in the radial direction is presented via fractal design and then implemented by EB-3D printing. This radial-gradient structure successfully mimics the radially gradual decrease in porosity of natural bone from cancellous bone to cortical bone. First, we create a design-to-fabrication workflow with embedding the graded data on basis of fractal design into digital processing to instruct the extrusion process of fractal-like scaffolds. Further, by a combination of suitable extruded inks, a series of bone-mimicking scaffolds with a 3-iteration fractal-like structure are fabricated to demonstrate their superiority, including radial porosity, mechanical property, and permeability. This study showcases a robust strategy to overcome the limitations of conventional EB-3D printers for the design and fabrication of functionally graded scaffolds, showing great potential in bone tissue engineering