Genetic variation in the hTAS2R38 taste receptor and food consumption among Finnish adults

Genetic variation in bitter taste receptors, such as hTAS2R38, may affect food preferences and intake. The aim of the present study was to investigate the association between bitter taste receptor haplotypes and the consumption of vegetables, fruits, berries and sweet foods among an adult Finnish population. A cross-sectional design utilizing data from the Cardiovascular Risk in Young Finns cohort from 2007, which consisted of 1,903 men and women who were 30-45 years of age from five different regions in Finland, was employed. DNA was extracted from blood samples, and hTAS2R38 polymorphisms were determined based on three SNPs (rs713598, rs1726866 and rs10246939). Food consumption was assessed with a validated food frequency questionnaire. The prevalence of the bitter taste-sensitive (PAV/PAV) haplotype was 11.3 % and that of the insensitive (AVI/AVI) haplotype was 39.5 % among this Finnish population. PAV homozygotic women consumed fewer vegetables than did the AVI homozygotic women, 269 g/day (SD 131) versus 301 g/day (SD 187), respectively, p = 0.03 (multivariate ANOVA). Furthermore, the intake of sweet foods was higher among the PAV homozygotes of both genders. Fruit and berry consumption did not differ significantly between the haplotypes in either gender. Individuals perceive foods differently, and this may influence their patterns of food consumption. This study showed that the hTAS2R38 taste receptor gene variation was associated with vegetable and sweet food consumption among adults in a Finnish population.Peer reviewe

Changes in objectively measured smoking in pregnancy by time and legislative changes in Finland: a retrospective cohort study

Objectives: To study the changes in prevalence, characteristics and outcomes of pregnant smokers over time and legislative changes.Design and setting: Retrospective nationwide cohort.Participants: Our study consisted of 9627 randomly selected pregnancies from the Finnish Maternity Cohort (1987-2011), with demographic characteristics and pregnancy and perinatal data obtained from the Medical Birth Registry and early pregnancy serum samples analysed for cotinine levels. Women were categorised based on their self-reported smoking status and measured cotinine levels (with >= 4.73 ng/mL deemed high). Data were stratified to three time periods based on legislative changes in the Tobacco Act.Primary and secondary outcome measures: Prevalence of pregnant smokers and demographics, and perinatal and pregnancy outcomes of pregnant smokers over time.Results: Overall, 71.6% of women were non-smokers, 16.2% were active cigarette smokers, 7.7% undisclosed smoking but had high cotinine levels and 4.5% were inactive cigarette smokers. The prevalence of active cigarette smokers decreased from mid-1990s onwards among women aged >= 30 years, probably due to the ban of cigarette smoking in most workplaces. We observed no changes in the prevalence of inactive smokers or women who undisclosed smoking by time or legislative changes. Women who undisclosed smoking had similar characteristics and perinatal outcomes as inactive and active smokers. Compared with non-smokers, women who undisclosed smoking were more likely to be young, unmarried, have a socioeconomic status lower than white-collar worker and have a preterm birth.Conclusions: Women who undisclosed smoking were very similar to pregnant cigarette smokers. We observed a reduction in the prevalence of active pregnant cigarette smokers after the ban of indoor smoking in workplaces and restaurants, mostly among women aged >= 30 years

Incidence of liver-related morbidity and mortality in a population cohort of non-alcoholic fatty liver disease

Background & Aims Non-alcoholic fatty liver disease (NAFLD) increases morbidity and mortality. However, patients in biopsy-based cohorts are highly selected and the absolute risks of liver- and non-liver outcomes in NAFLD in population remains undefined. We analysed both liver-related and non-liver-related outcomes in Finnish population cohorts of NAFLD. Methods We included 10 993 individuals (6707 men, mean age 53.3 +/- 12.6 years) with NAFLD (fatty liver index >= 60) from the Finnish population-based FINRISK and Health 2000 studies. Liver fibrosis was assessed by the dAAR score, and genetic risk by a recent polygenic risk score (PRS-5). Incident liver-related outcomes, cardiovascular disease (CVD), cancer and chronic kidney disease (CKD) were identified through linkage with national registries. Results Mean follow-up was 12.1 years (1128 069 person-years). The crude incidence rate of liver-related outcomes in NAFLD was 0.97/1000 person-years. The cumulative incidence increased with age, being respectively 2.4% and 1.5% at 20 years in men and women aged 60 years at baseline, while the relative risks for CVD and cancer were 9-16 times higher. The risk of CKD exceeded that of liver outcomes at a baseline age around 50 years. 20-year cumulative incidence of liver-related outcomes was 4.3% in the high, and 1.5% in the low PRS-5 group. The dAAR score associated with liver outcomes, but not with extra-hepatic outcomes. Conclusion The absolute risk of liver-related outcomes in NAFLD is low, with much higher risk of CVD and cancer, emphasizing the need for more individualized and holistic risk-stratification in NAFLD.Peer reviewe

Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Health and Social Care Educators' Competence in Digital Collaborative Learning: A Cross-Sectional Survey

The ongoing change from traditional pedagogy to digital collaborative learning requires a new mode of teaching, learning, and educators' responsibilities. For competence in digitally mediated teaching, educators need understanding of how to provide appropriate digital environment to learn collectively and individually. The aim of this study was to describe and explore health and social care educators' perceptions of their current level of competence in digital collaborative learning and identify distinct educators' profiles. Data were collected via cross-sectional survey from educators in 21 universities of applied science and eight vocational colleges in Finland using an instrument covering two subdimensions: educators' competence in fostering construction of knowledge in digital collaborative learning, and supporting students in individualized collaborative learning. The data were analyzed by statistical methods. Three significantly differing clusters of educators' profiles were identified, and a significant association between type of current work organization and their self-reported competence in digital collaborative learning was found. The vocational college educators rated their competence in fostering construction of knowledge in digital collaborative learning as significantly lower than higher education educators. There were also remarkable differences in competence in supporting students' individual collaborative learning. To provide such support, sufficient competence in teaching in digital learning environment is essential, and our study highlights clear needs to enhance this competence

Structural Mechanism of S-Adenosyl Methionine Binding to Catechol O-Methyltransferase

Methyltransferases possess a homologous domain that requires both a divalent metal cation and S-adenosyl-L-methionine (SAM) to catalyze its reactions. The kinetics of several methyltransferases has been well characterized; however, the details regarding their structural mechanisms have remained unclear to date. Using catechol O-methyltransferase (COMT) as a model, we perform discrete molecular dynamics and computational docking simulations to elucidate the initial stages of cofactor binding. We find that COMT binds SAM via an induced-fit mechanism, where SAM adopts a different docking pose in the absence of metal and substrate in comparison to the holoenzyme. Flexible modeling of the active site side-chains is essential for observing the lowest energy state in the apoenzyme; rigid docking tools are unable to recapitulate the pose unless the appropriate side-chain conformations are given a priori. From our docking results, we hypothesize that the metal reorients SAM in a conformation suitable for donating its methyl substituent to the recipient ligand. The proposed mechanism enables a general understanding of how divalent metal cations contribute to methyltransferase function

Metabolic profiling of alcohol consumption in 9778 young adults

Background: High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults. Methods: Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. Results: Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P<0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U-shaped associations with alcohol consumption. Results were coherent for men and women, consistent across the three cohorts and similar if adjusting for body mass index, smoking and physical activity. The metabolic changes accompanying change in alcohol intake during follow-up resembled the cross-sectional association pattern (R-2 = 0.83, slope = 0.7260.04). Conclusions: Alcohol consumption is associated with a complex metabolic signature, including aberrations in multiple biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with long-term changes in alcohol consumption. These results elucidate the double-edged effects of alcohol on cardiovascular risk.Peer reviewe

Lipoprotein subclass metabolism in nonalcoholic steatohepatitis

Peer reviewe

Role of liposome and peptide in the synergistic enhancement of transfection with a lipopolyplex vector

Lipopolyplexes are of widespread interest for gene therapy due to their multifunctionality and high transfection efficiencies. Here we compared the biological and biophysical properties of a lipopolyplex formulation with its lipoplex and polyplex equivalents to assess the role of the lipid and peptide components in the formation and function of the lipopolyplex formulation. We show that peptide efficiently packaged plasmid DNA forming spherical, highly cationic nanocomplexes that are taken up efficiently by cells. However, transgene expression was poor, most likely due to endosomal degradation since the polyplex lacks membrane trafficking properties. In addition the strong peptide-DNA interaction may prevent plasmid release from the complex and so limit plasmid DNA availability. Lipid/DNA lipoplexes, on the other hand, produced aggregated masses that showed poorer cellular uptake than the polyplex but contrastingly greater levels of transgene expression. This may be due to the greater ability of lipoplexes relative to polyplexes to promote endosomal escape. Lipopolyplex formulations formed spherical, cationic nanocomplexes with efficient cellular uptake and significantly enhanced transfection efficiency. The lipopolyplexes combined the optimal features of lipoplexes and polyplexes showing optimal cell uptake, endosomal escape and availability of plasmid for transcription, thus explaining the synergistic increase in transfection efficiency