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

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

Missing Teeth Predict Incident Cardiovascular Events, Diabetes, and Death

Periodontitis, the main cause of tooth loss in the middle-aged and elderly, associates with the risk of atherosclerotic vascular disease. The objective was to study the capability of the number of missing teeth in predicting incident cardiovascular diseases (CVDs), diabetes, and all-cause death. The National FINRISK 1997 Study is a Finnish population-based survey of 8,446 subjects with 13 y of follow-up. Dental status was recorded at baseline in a clinical examination by a trained nurse, and information on incident CVD events, diabetes, and death was obtained via national registers. The registered CVD events included coronary heart disease events, acute myocardial infarction, and stroke. In Cox regression analyses, having >= 5 teeth missing was associated with 60% to 140% increased hazard for incident coronary heart disease events (P = 9 missing teeth. No association with stroke was observed. Adding information on missing teeth to established risk factors improved risk discrimination of death (P = 0.0128) and provided a statistically significant net reclassification improvement for all studied end points. Even a few missing teeth may indicate an increased risk of CVD, diabetes, or all-cause mortality. When individual risk factors for chronic diseases are assessed, the number of missing teeth could be a useful additional indicator for general medical practitioners.Peer reviewe

The impact of the Val158Met catechol-O-methyltransferase genotype on neural correlates of sad facial affect processing in patients with bipolar disorder and their relatives

Background - The Met allele of the catechol-O-methyltransferase (COMT) valine-to-methionine (Val158Met) polymorphism is known to affect dopamine-dependent affective regulation within amygdala-prefrontal cortical (PFC) networks. It is also thought to increase the risk of a number of disorders characterized by affective morbidity including bipolar disorder (BD), major depressive disorder (MDD) and anxiety disorders. The disease risk conferred is small, suggesting that this polymorphism represents a modifier locus. Therefore our aim was to investigate how the COMT Val158Met may contribute to phenotypic variation in clinical diagnosis using sad facial affect processing as a probe for its neural action. Method - We employed functional magnetic resonance imaging to measure activation in the amygdala, ventromedial PFC (vmPFC) and ventrolateral PFC (vlPFC) during sad facial affect processing in family members with BD (n=40), MDD and anxiety disorders (n=22) or no psychiatric diagnosis (n=25) and 50 healthy controls. Results - Irrespective of clinical phenotype, the Val158 allele was associated with greater amygdala activation and the Met allele with greater signal change in the vmPFC and vlPFC. Signal changes in the amygdala and vmPFC were not associated with disease expression. However, in the right vlPFC the Met158 allele was associated with greater activation in all family members with affective morbidity compared with relatives without a psychiatric diagnosis and healthy controls. Conclusions - Our results suggest that the COMT Val158Met polymorphism has a pleiotropic effect within the neural networks subserving emotional processing. Furthermore the Met158 allele further reduces cortical efficiency in the vlPFC in individuals with affective morbidity

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

Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease

Background & Aims: Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However, there is still a missing hereditability indicating that other genetic variants are yet to be discovered. Methods: To find genes involved in FLD, we first examined the association of missense and nonsense variants with alanine aminotransferase at an exome-wide level in 425,671 participants from the UK Biobank. We then validated genetic variants with liver fat content in 8930 participants in whom liver fat measurement was available, and replicated 2 genetic variants in 3 independent cohorts comprising 2621 individuals with available liver biopsy. Results: We identified 190 genetic variants independently associated with alanine aminotransferase after correcting for multiple testing with Bonferroni method. The majority of these variants were not previously associated with this trait. Among those associated, there was a striking enrichment of genetic variants influencing lipid metabolism. We identified the variants rs2792751 in GPAM/GPAT1, the gene encoding glycerol-3-phosphate acyltransferase, mitochondrial, and rs429358 in APOE, the gene encoding apolipoprotein E, as robustly associated with liver fat content and liver disease after adjusting for multiple testing. Both genes affect lipid metabolism in the liver. Conclusions: We identified 2 novel genetic variants in GPAM and APOE that are robustly associated with steatosis and liver damage. These findings may help to better elucidate the genetic susceptibility to FLD onset and progression

Body Size at Birth Is Associated with Food and Nutrient Intake in Adulthood

WOS:000309517300090Peer 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