Search

Study Question: Does having a male co-twin, older brothers, or sons lead to an increased probability of persistent male microchimerism in female members of twin pedigrees?Summary Answer: The presence of a male co-twin did not increase risk of male microchimerism and the prevalence of male microchimerism was not explained by having male offspring or by having an older brother.What Is Known Already: Microchimerism describes the presence of cells within an organism that originate from another zygote and is commonly described as resulting from pregnancy in placental mammals. It is associated with diseases with a female predilection including autoimmune diseases and pregnancy-related complications. However, microchimerism also occurs in nulliparous women; signifying gaps in the understanding of risk factors contributing to persistent microchimerism and the origin of the minor cell population.Study Design, Size, Duration: This cross-sectional study composed of 446 adult female participants of the Netherlands Twin Register (NTR).Participants/materials, Setting, Methods: Participants included in the study were female monozygotic (MZ) twins, female dizygotic same-sex twins and females of dizygotic opposite-sex twin pairs, along with the mothers and sisters of these twins. Peripheral blood samples collected from adult female participants underwent DNA extraction and were biobanked prior to the study. To detect the presence of male-origin microchimerism, DNA samples were tested for the relative quantity of male specific Y chromosome gene DYS14 compared to a common β-globin gene using a highly sensitive quantitative PCR assay.Main Results and the Role Of Chance: We observed a large number of women (26.9%) having detectable male microchimerism in their peripheral blood samples. The presence of a male co-twin did not increase risk of male microchimerism (odds ratio (OR) = 1.23: SE 0.40, P = 0.61) and the prevalence of male microchimerism was not explained by having male offspring (OR 0.90: SE 0.19, P = 0.63) or by having an older brother (OR = 1.46: SE 0.32, P = 0.09). The resemblance (correlation) for the presence of microchimerism was similar (P = 0.66) in MZ pairs (0.27; SE 0.37) and in first-degree relatives (0.091; SE 0.092). However, age had a positive relationship with the presence of male microchimerism (P = 0.02).Limitations, Reasons For Caution: After stratifying for variables of interest, some participant groups resulted in a low numbers of subjects. We investigated microchimerism in peripheral blood due to the proposed mechanism of cell acquisition via transplacental blood exchange; however, this does not represent global chimerism in the individual and microchimerism may localize to numerous other tissues.Wider Implications Of the Findings: Immune regulation during pregnancy is known to mitigate allosensitization and support tolerance to non-inherited antigens found on donor cells. While unable to identify a specific source that promotes microchimerism prevalence within pedigrees, this study points to the underlying complexities of natural microchimerism in the general population. These findings support previous studies which have identified the presence of male microchimerism among women with no history of pregnancy, suggesting alternative sources of microchimerism. The association of detectable male microchimerism with age is suggestive of additional factors including time, molecular characteristics and environment playing a critical role in the prevalence of persistent microchimerism. The present study necessitates investigation into the molecular underpinnings of natural chimerism to provide insight into women's health, transplant medicine and immunology.Study Funding/competing Interest(s): This work is funded by Royal Netherlands Academy of Science Professor Award (PAH/6635 to D.I.B.); The Netherlands Organisation for Health Research and Development (ZonMw)-Genotype/phenotype database for behavior genetic and genetic epidemiological studies (ZonMw 911-09-032); Biobanking and Biomolecular Research Infrastructure (BBMRI-NL, 184.021.007; 184.033.111); The Netherlands Organisation for Scientific Research (NWO)-Netherlands Twin Registry Repository (NWO-Groot 480-15-001/674); the National Institutes of Health-The Rutgers University Cell and DNA Repository cooperative agreement (NIMH U24 MH068457-06), Grand Opportunity grants Integration of genomics and transcriptomics in normal twins and major depression (NIMH 1RC2 MH089951-01), and Developmental trajectories of psychopathology (NIMH 1RC2 MH089995); and European Research Council-Genetics of Mental Illness (ERC 230374). C.B.L. declares a competing interest as editor-in-chief of Human Reproduction and his department receives unrestricted research grants from Ferring, Merck and Guerbet. All remaining authors have no conflict-of-interest to declare in regards to this work.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Introduction: FTND (Fagerstrӧm test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported.Methods: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts.Results: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND.Conclusions: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND.Implications: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways. [ABSTRACT FROM AUTHOR]

Aims: This paper presents updated prevalence estimates of awareness, ever‐use, and current use of nicotine vaping products (NVPs) from 14 International Tobacco Control Policy Evaluation Project (ITC Project) countries that have varying regulations governing NVP sales and marketing. Design, Setting, Participants and Measurements: A cross‐sectional analysis of adult (≥ 18 years) current smokers and ex‐smokers from 14 countries participating in the ITC Project. Data from the most recent survey questionnaire for each country were included, which spanned the period 2013–17. Countries were categorized into four groups based on regulations governing NVP sales and marketing (allowable or not), and level of enforcement (strict or weak where NVPs are not permitted to be sold): (1) most restrictive policies (MRPs), not legal to be sold or marketed with strict enforcement: Australia, Brazil, Uruguay; (2) restrictive policies (RPs), not approved for sale or marketing with weak enforcement: Canada, Malaysia, Mexico, New Zealand; (3) less restrictive policies (LRPs), legal to be sold and marketed with regulations: England, the Netherlands, Republic of Korea, United States; and (4) no regulatory policies (NRPs), Bangladesh, China, Zambia. Countries were also grouped by World Bank Income Classifications. Country‐specific weighted logistic regression models estimated adjusted NVP prevalence estimates for: awareness, ever/current use, and frequency of use (daily versus non‐daily). Findings NVP awareness and use were lowest in NRP countries. Generally, ever‐ and current use of NVPs were lower in MRP countries (ever‐use = 7.1–48.9%; current use = 0.3–3.5%) relative to LRP countries (ever‐use = 38.9–66.6%; current use = 5.5–17.2%) and RP countries (ever‐use = 10.0–62.4%; current use = 1.4–15.5%). NVP use was highest among high‐income countries, followed by upper–middle‐income countries, and then by lower–middle‐income countries. Conclusions: With a few exceptions, awareness and use of nicotine vaping products varied by the strength of national regulations governing nicotine vaping product sales/marketing, and by country income. In countries with no regulatory policies, use rates were very low, suggesting that there was little availability, marketing and/or interest in nicotine vaping products in these countries where smoking populations are predominantly poorer. The higher awareness and use of nicotine vaping products in high income countries with moderately (e.g. Canada, New Zealand) and less (e.g. England, United States) restrictive policies, is likely due to the greater availability and affordability of nicotine vaping products. [ABSTRACT FROM AUTHOR]

Our principal ethical concern is that children have greatly differing opportunities to have their developmental needs addressed in the custody process. We illustrate this variation with example cases in five different adult contexts: custodial parent, relocates; natural father disputes an adoption; gay parents break up; “psychological parents” come forward to claim custody or visitation; and the Indian Child Welfare Act of 1978 is invoked and may disrupt a placement. We acknowledge and then evaluate in relation to our cases, the recent guidelines for custody issued by the American Law Institute ( Principles of the Law of Family Dissolution: Analysis and Recommendations, 2002). Our recommendations for an ethical process include making the child a legal player. [ABSTRACT FROM AUTHOR]

Background. Life expectancy of people with intellectual disabilities (IDs) is rapidly normalizing, as are prevalences of age-related cardiovascular disease in this group. We investigated the prevalence of the metabolic syndrome in the older population with ID and associations with patient characteristics.Methods. Prevalence of the metabolic syndrome, according to National Cholesterol Education Program-Adult Treatment Panel III criteria, was assessed with standardized physical examinations in 470 Dutch adults with ID, aged ≥50 years, who receive residential care from three Dutch care providing organizations. Because of skewing towards an overrepresentation of females and more moderate to severe ID in the study population, reweighting was applied to obtain a representative population prevalence. Correlations with patient characteristics were analysed with logistic regression analyses.Results. Four hundred and twelve participants completed all assessments. The weighted prevalence of the metabolic syndrome was 25.1% [95% confidence interval (CI) 21.0–29.3%], with a significantly higher risk for people with mild ID.Conclusions. The prevalence of the metabolic syndrome in the population with ID is significantly higher than that in the general Dutch population aged ≥50 years (15.7%, 95% CI 13.5–17.9%). [ABSTRACT FROM PUBLISHER]

Background: Our study evaluated the short-term impact of introducing European Union's tobacco pictorial health warnings (PHWs).Methods: Longitudinal data were collected at two time-points from adult smokers, participating in the International Tobacco Control (ITC) surveys, conducted in the Netherlands, Australia, Canada, the United Kingdom and the United States. In the Netherlands, textual health warnings (THWs) were replaced by PHWs between both time-points. Health warning policies did not change in the other countries. Data from continuing smokers were used (N = 3,487) and analyzed using Generalized Estimating Equations.Results: Between both time-points, only Dutch smokers showed increases in noticing health warnings (β = 0.712, p < 0.001), self-reports of health warnings leading to a cognitive response such as thinking about smoking health-risks (SHRs) (OR = 1.834, p < 0.001), knowledge about SHRs (β = 0.369, p < 0.001), and avoiding health warnings (OR = 9.869, p < 0.001). However, Dutch smokers showed no changes in attitude towards smoking (β = 0.035, p = 0.518), intention to quit smoking (OR = 0.791, p = 0.157), self-efficacy to quit smoking (β=-0.072, p = 0.286), or reporting that health warnings helped them to resist having a cigarette (OR = 1.091, p = 0.714).Conclusions: Results suggest that introducing the European PHWs was effective in provoking changes closely related to health warnings, but there was no direct impact on variables more closely related to smoking cessation. [ABSTRACT FROM AUTHOR]