Publications

The global epidemic of obesity and physical inactivity may have detrimental implications for young people's cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents' academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents' academic achievement via physical inactivity (B = -0.023, 95% confidence interval = -0.031, -0.015) and obesity (B = -0.025, 95% confidence interval = -0.039, -0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents' academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement.

The objective of this study was to assess the serological association between previous Chlamydia trachomatis infection and subfertility in a general population sample. A nested case ( n =493)-control ( n =986) study in a population-based birth cohort consisting of 12058 live births from the year 1966 was conducted. The analysis was restricted to those 6007 cohort members who replied to a postal inquiry and participated in a health examination including blood samples at the age of 31 years. The presence of C. trachomatis -specific serum IgG antibodies was screened by a synthetic peptide-based enzyme-linked immunosorbent assay. All the positive sera were further tested by the microimmunofluorescence method using immunotype pools and individual immunotypes of C. trachomatis as antigens. An association was found between the detection of immunotype-specific C. trachomatis antibodies and subfertility both in men and women. The results of the present study confirm the serological association between past C. trachomatis infections and subfertility in male or female partners of the couple in the population-based sample.

No abstract is provided for this article.

Abstract Attention-deficit/hyperactivity disorder (ADHD) often co-occurs with obesity, however, the potential causality between the traits remains unclear. We examined both genetic and prenatal evidence for causality using Mendelian Randomisation (MR) and polygenic risk scores (PRS). We conducted bi-directional MR on ADHD liability and six obesity-related traits using summary statistics from the largest available meta-analyses of genome-wide association studies. We also examined the shared genetic aetiology between ADHD symptoms (inattention and hyperactivity) and body mass index (BMI) by PRS association analysis using longitudinal data from Northern Finland Birth Cohort 1986 (NFBC1986, n = 2984). Lastly, we examined the impact of the prenatal environment by association analysis of maternal pre-pregnancy BMI and offspring ADHD symptoms, adjusted for PRS of both traits, in NFBC1986 dataset. Through MR analyses, we found evidence for bidirectional causality between ADHD liability and obesity-related traits. PRS association analyses showed evidence for genetic overlap between ADHD symptoms and BMI. We found no evidence for a difference between inattention and hyperactivity symptoms, suggesting that neither symptom subtype is driving the association. We found evidence for association between maternal pre-pregnancy BMI and offspring ADHD symptoms after adjusting for both BMI and ADHD PRS (association p -value = 0.027 for inattention, p = 0.008 for hyperactivity). These results are consistent with the hypothesis that the co-occurrence between ADHD and obesity has both genetic and prenatal environmental origins.

Abstract Background An accumulating body of evidence suggests that the number of apolipoprotein B-containing particles (ApoB-P) is more predictive of cardiovascular risk than their lipid content. However, it is unclear if this association is consistent across different lipoprotein types and sizes. Purpose We aimed to evaluate if particle type and size are associated with incident myocardial infarction (MI) beyond ApoB-P count. Moreover, we aimed to determine if the risk associated with lipoprotein(a) is additive to that of ApoB-P. Methods This prospective cohort study included 96,126 participants without prior history of stroke, coronary or peripheral artery disease or use of lipid-lowering medication from the UK Biobank. Count and size of VLDL, IDL, LDL, and HDL, as well as ApoB level and total ApoB-P count were measured in non-fasting plasma samples by nuclear magnetic resonance platform. Lipoprotein(a) was measured by immunoturbidimetric assay. We explored associations between these lipoprotein markers and incident MI using Cox proportional hazard models adjusted sequentially for clinical covariates, HDL count and size, and ApoB-P. Results Over a median follow-up of 12.1 years, 1702 participants had incident MI. In unadjusted models, 1-SD increases in ApoB-P count, ratio of VLDL to (LDL+IDL) particle counts, VLDL size and lipoprotein(a) were associated with a higher risk of MI, while LDL size was associated with a lower risk of MI (Table 1). When adjusting for clinical covariates and lipid parameters, only ApoB-P and lipoprotein(a) remained significantly associated with a higher risk of MI (HR: 1.40 [1.32; 1.48] and 1.20 [1.14; 1.27], respectively). Adjusted restricted cubic splines confirmed findings from linear trend Cox models (Figure 1). ApoB-P count was highly correlated with ApoB level (r=0.99), and replication of analyses replacing one for another revealed no change in results. Conclusion The risk of MI is independently associated with the total particle count of all ApoB-P, and not the size or type of these lipoproteins. ApoB level can be used as a very accurate surrogate of ApoB-P count in the clinical setting. Lipoprotein(a) is associated with MI risk independently of total particle count, and therefore, the combination of ApoB and lipoprotein(a) may provide the optimal clinical evaluation of lipid-mediated MI risk. Funding Acknowledgement Type of funding sources: None.

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni < 1.06 x 10 −7 ). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

OBJECTIVE We examined the relationship between ultra-processed food (UPF) intake and type 2 diabetes (T2D) risk among 3 large U.S. cohorts, conducted a meta-analysis of prospective cohort studies, and assessed meta-evidence quality. RESEARCH DESIGN AND METHODS We included 71,871 women from the Nurses’ Health Study, 87,918 women from the Nurses’ Health Study II, and 38,847 men from the Health Professional Follow-Up Study. Diet was assessed using food frequency questionnaires and UPF was categorized per the NOVA classification. Associations of total and subgroups of UPF with T2D were assessed using Cox proportional hazards models. We subsequently conducted a meta-analysis of prospective cohort studies on total UPF and T2D risk, and assessed meta-evidence quality using the NutriGrade scoring system. RESULTS Among the U.S. cohorts (5,187,678 person-years; n = 19,503 T2D cases), the hazard ratio for T2D comparing extreme quintiles of total UPF intake (percentage of grams per day) was 1.46 (95% CI 1.39–1.54). Among subgroups, refined breads; sauces, spreads, and condiments; artificially and sugar-sweetened beverages; animal-based products; and ready-to-eat mixed dishes were associated with higher T2D risk. Cereals; dark and whole-grain breads; packaged sweet and savory snacks; fruit-based products; and yogurt and dairy-based desserts were associated with lower T2D risk. In the meta-analysis (n = 415,554 participants; n = 21,932 T2D cases), each 10% increment in total UPF was associated with a 12% (95% CI 10%–13%) higher risk. Per NutriGrade, high-quality evidence supports this relationship. CONCLUSIONS High-quality meta-evidence shows that total UPF consumption is associated with higher T2D risk. However, some UPF subgroups were associated with lower risk in the U.S. cohorts.

Magnetic levitation (MagLev) of diamagnetic or weakly paramagnetic materials suspended in a paramagnetic solution in a magnetic field gradient provides a simple method to measure the density of small samples of solids or liquids. One major limitation of this method, thus far, has been an inability to measure or manipulate materials outside of a narrow range of densities (0.8 g/cm(3) < ρ < 2.3 g/cm(3)) that are close in density to the suspending, aqueous medium. This paper explores a simple method-"tilted MagLev"-to increase the range of densities that can be levitated magnetically. Tilting the MagLev device relative to the gravitational vector enables the magnetic force to be decreased (relative to the magnetic force) along the axis of measurement. This approach enables many practical measurements over the entire range of densities observed in matter at ambient conditions-from air bubbles (ρ ≈ 0) to osmium and iridium (ρ ≈ 23 g/cm(3)). The ability to levitate, simultaneously, objects with a broad range of different densities provides an operationally simple method that may find application to forensic science (e.g., for identifying the composition of miscellaneous objects or powders), industrial manufacturing (e.g., for quality control of parts), or resource-limited settings (e.g., for identifying and separating small particles of metals and alloys).

Electrophysiological recording technologies can provide critical insight into the function of the nervous system and other biological tissues. Standard silicon-based probes have limitations, including single-sided recording sites and intrinsic instabilities due to the probe stiffness. Here, we demonstrate high-performance neural recording using double-sided three-dimensional (3D) electrodes integrated in an ultraflexible bioinspired open mesh structure, allowing electrodes to sample fully the 3D interconnected tissue of the brain. In vivo electrophysiological recording using 3D electrodes shows statistically significant increases in the number of neurons per electrode, average spike amplitudes, and signal to noise ratios in comparison to standard two-dimensional electrodes, while achieving stable detection of single-neuron activity over months. The capability of these 3D electrodes is further shown for chronic recording from retinal ganglion cells in mice. This approach opens new opportunities for a comprehensive 3D interrogation, stimulation, and understanding of the complex circuitry of the brain and other electrogenic tissues in live animals over extended time periods.

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

The authors investigated the shape, sex- and age-dependency, and possible confounding of the association between birth weight and systolic blood pressure (SBP) in 197,954 adults from 20 Nordic cohorts (birth years 1910-1987), one of which included 166,249 Swedish male conscripts. Random-effects meta-regression analyses were performed on estimates obtained from age- and sex-stratified analyses within each of the cohorts. There was an inverse association between birth weight and SBP, irrespective of adjustment for concurrent body mass index. The association was linear for males, but for females with a birth weight greater than 4 kg, SBP increased with birth weight (p < 0.01). The association was stronger in the older age groups (p < 0.05), although this could have been a birth cohort effect. The association was stronger among females than among males (p = 0.005) when birth weight was less than or equal to 4 kg. The estimated effect of birth weight on SBP at age 50 years was -1.52 mmHg/kg (95% confidence interval: -2.27, -0.77) in men and -2.80 mmHg/kg (95% confidence interval: -3.85, -1.76) in women. Exclusion of the Swedish conscripts produced nearly identical results. This meta-analysis supports the evidence of an inverse birth weight-SBP association, regardless of adjustment for concurrent body size. It also reveals important heterogeneity in the shape and strength of the association by sex and age.