Explore the vast range of titles available.

The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon sequencing during the first year of life with subsequent risk of asthma in 690 participants, that 1-year-old children with an immature microbial composition have an increased risk of asthma at age 5 years. This association is only apparent among children born to asthmatic mothers, suggesting that lacking microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children. Colonization of commensal bacteria is thought to impact immune development, especially in the earliest years of life. Here, the authors show, by analyzing the development of the gut microbiome of 690 children, that microbial composition at the age of 1 year is associated with asthma diagnosed in the first 5 years of life.

Supplementation with fish oil–derived fatty acids during pregnancy reduced the incidence of cases of persistent wheeze or asthma in offspring. The incidence of asthma and wheezing disorders has more than doubled in westernized countries in recent decades. 1 These conditions often originate in early childhood 2 and currently affect one in five young children. 3 Concomitantly, the increased use of vegetable oils in cooking and of grain in the feeding of livestock has resulted in an increase in the intake of n−6 polyunsaturated fatty acids and a decrease in the intake of n−3 polyunsaturated fatty acids, especially the long-chain polyunsaturated fatty acids (LCPUFAs) — eicosapentaenoic acid (20:5n–3, EPA) and docosahexaenoic acid (22:6n–3, DHA) — found in cold-water fish. 4 Observational studies have suggested an . . .

The originally published version of this Article contained an incorrect version of Figure 3 that was introduced following peer review and inadvertently not corrected during the production process. Both versions contain the same set of abundance data, but the incorrect version has the children’s asthma status erroneously disconnected from the abundance data, thereby producing the non-representative p values and graphic presentations. These errors have now been rectified, with the correct version of Figure 3 replaced in both the PDF and HTML versions of the Article.

Vitamin D deficiency and elevated high sensitivity C-reactive protein (hs-CRP) have been associated with several health outcomes, but knowledge on early life trajectories and association between 25 hydroxyvitamin D (25(OH)D) and hs-CRP is lacking. We investigated the association between longitudinal measurements of 25(OH)D and hs-CRP, respectively, from pregnancy to childhood and throughout childhood in two Danish mother–child cohorts—the COPSAC2010 and COPSAC2000. In COPSAC2010, there was an association between 25(OH)D concentrations at week 24 in pregnancy and at age 6 months in childhood (n = 633): estimate (95% CI); 0.114 (0.041;0.187), p = 0.002, and between 25(OH)D at age 6 months and 6 years (n = 475): 0.155 (0.083;0.228), p < 0.001. This was also demonstrated in the COPSAC2000 cohort between 25(OH)D concentrations in cord blood and at age 4 years (n = 188): 0.294 (0.127;0.461), p < 0.001 and at age 6 months and 4 years (n = 264): 0.260 (0.133;0.388), p < 0.001. In COPSAC2000, we also found an association between hs-CRP at age 6 months and 12 years in childhood (n = 232): 0.183 (0.076;0.289), p < 0.001. Finally, we found a negative association between the cross-sectional measurements of 25(OH)D and hs-CRP at age 6 months (n = 613) in COPSAC2010: −0.004 (−0.008;−0.0004), p = 0.030, but this was not replicated in COPSAC2000. In this study, we found evidence of associations across timepoints of 25(OH)D concentrations from mid-pregnancy to infancy and through childhood and associations between hs-CRP levels during childhood, although with weak correlations. We also found a negative cross-sectional association between 25(OH)D and hs-CRP concentrations in COPSAC2010 proposing a role of vitamin D in systemic low-grade inflammation, though this association was not present in COPSAC2000.

Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Type 2 diabetes and glycemic traits. This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (β = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.

The sympathetic nervous system and its neurotransmitter effectors are undeniably important to blood pressure control. We made the novel discovery that perivascular adipose tissue (PVAT) contains significant concentrations of catecholamines. We hypothesized that PVAT contains sufficient releasable catecholamines to affect vascular function. High‐pressure liquid chromatography, isometric contractility, immunohistochemistry, whole animal approaches, and pharmacology were used to test this hypothesis. In normal rat thoracic aorta and superior mesenteric artery, the indirect sympathomimetic tyramine caused a concentration‐dependent contraction that was dependent on the presence of PVAT. Tyramine stimulated release of norepinephrine (NA), dopamine (DA) and the tryptamine serotonin (5‐hydroxytryptamine [5‐HT]) from PVAT isolated from both arteries. In both arteries, tyramine‐induced concentration‐dependent contraction was rightward‐shifted and reduced by the noradrenaline transporter inhibitor nisoxetine (1 μmol/L), the vesicular monoamine transporter inhibitor tetrabenazine (10 μmol/L), and abolished by the α adrenoreceptor antagonist prazosin (100 nmol/L). Inhibitors of the DA and 5‐HT transporter did not alter tyramine‐induced, PVAT‐dependent contraction. Removal of the celiac ganglion as a neuronal source of catecholamines for superior mesenteric artery PVAT did not significantly reduce the maximum or shift the concentration‐dependent contraction to tyramine. Electrical field stimulation of the isolated aorta was not affected by the presence of PVAT. These data suggest that PVAT components that are independent of sympathetic nerves can release NA in a tyramine‐sensitive manner to result in arterial contraction. Because PVAT is intimately apposed to the artery, this raises the possibility of local control of arterial function by PVAT catecholamines. e00041

Chornobyl Thyroid Diseases Study Group of Belarus, Ukraine, and the USA. A Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident: Objectives, Design and Methods. Radiat. Res. 161, 481–492 (2004). The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and γ rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly 131I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose–response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.