Birth weight variants are associated with variable fetal intrauterine growth from 20 weeks of gestation.

Fetal intrauterine growth is influenced by complex interactions between the maternal genes, environment and fetal genes. The aim of this study was to assess the effect of GWAS-identified genetic variants associated with birth weight on intrauterine fetal growth in 665 children. Fetal growth was estimated by two-dimensional ultrasound scans at 20, 25 and 32 weeks of gestation and growth trajectories were modeled using mixed linear regression. A genetic risk score (GRS) of birth weight-raising variants was associated with intrauterine growth showing an attenuating effect on the unconditional daily reduction in proportional weight gain of 8.92 × 10-6 percentage points/allele/day (p = 2.0 × 10-4), corresponding to a mean difference of 410 g at 40 weeks of gestation between a child with lowest and highest GRS. Eight variants were independently associated with intrauterine growth throughout the pregnancy, while four variants were associated with fetal growth in the periods 20-25 or 25-32 weeks of gestation, indicating that some variants may act in specific time windows during pregnancy. Four of the intrauterine growth variants were associated with type 2 diabetes, hypertension or BMI in the UK Biobank, which may provide basis for further understanding of the link between intrauterine growth and later risk of metabolic disease.

Genetic predisposition to adiposity is associated with increased objectively assessed sedentary time in young children.

Increased sedentariness has been linked to the growing prevalence of obesity in children, but some longitudinal studies suggest that sedentariness may be a consequence rather than a cause of increased adiposity. We used Mendelian randomization to examine the causal relations between body mass index (BMI) and objectively assessed sedentary time and physical activity in 3-8 year-old children from one Finnish and two Danish cohorts [NTOTAL=679]. A genetic risk score (GRS) comprised of 15 independent genetic variants associated with childhood BMI was used as the instrumental variable to test causal effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.

Chromosomal aberrations in 130 patients with multiple myeloma studied by interphase FISH: diagnostic and prognostic relevance.

The study described the molecular cytogenetic characterization of myeloma cells in 130 patients via interphase fluorescence in situ hybridization. Nine repetitive DNA probes (for chromosomes 3, 7, 9, 11, 15, 17, 18, X, and Y) as well as seven single-copy DNA probes (for chromosomes 13, 17, 21, and two each for chromosomes 5 and 22) were used for the hybridizations. Using this panel of probes, we were able to show aberrations in 86% of patients. Most of them had one to three aberrations. There was a distinct correlation between the number of aberrations per patient and the tumor stage. Thus, the proportion of patients with 8-12 aberrations increased from 16% in stage II to 26% in stage III. There were marked differences among the chromosomes with respect to the prevalence of genomic losses and gains and deletions of gene loci. Chromosomes 3, 5, 7, 9, 11, 15, and 21 showed a preference for genomic gains. Losses were most often found for chromosomes 13 and 17 (locus specific) as well as for the X and Y chromosomes. The frequency of monosomies and trisomies were approximately the same for chromosomes 15 and 18, which indicates a skewed pattern of distribution. We found two specific aberrations that caused distinct changes in the survival rates of the patients: deletion 13q14 (28% of patients) and translocation of the IGH locus 14q32 (79% of 39 patients who were analyzed separately). The results obtained in this study yielded data of extremely relevant prognostic value.

Treatment of warfarin-associated coagulopathy with oral vitamin K: a randomised controlled trial.

BACKGROUND: Warfarin-associated coagulopathy is a frequent clinical complication. We aimed to assess whether treatment with vitamin K is safe and more effective than placebo in rapidly lowering the international normalised ratio (INR) into the therapeutic range in over anticoagulated patients receiving warfarin. METHODS: We did a multicentre, double-blind, placebo-controlled, randomised trial in five tertiary care hospitals. In this study, patients receiving warfarin who had an INR value between 4.5 and 10.0, and who did not have an indication for the immediate normalisation of their INR, had their warfarin withheld, and were randomly allocated to receive either 1 mg of vitamin K or placebo orally. The primary outcome measure was the INR value on the day after treatment. Secondary outcome measures included INR values on subsequent days, and the risk of haemorrhage and recurrent thrombosis over a 3 month follow-up period. FINDINGS: Patients given vitamin K had a more rapid decrease in the INR than those given placebo (25 of 45 (56%] vs nine of 44 [20%] patients with INR values of 1.8-3.2 on the day after treatment, respectively, p=0.001; odds ratio [OR] 0.21, 95% CI 0.07-0.57). Fewer patients given vitamin K had bleeding episodes during the follow-up period than those given placebo (two [4%] vs eight [17%] patients, respectively, p=0.050; OR 0.87, 95% CI 0.019-0.999). INTERPRETATION: Low dose oral vitamin K is more effective than placebo for the rapid lowering of raised INR values in patients taking warfarin.