Differential methylation of the arsenic (III) methyltransferase promoter according to arsenic exposure

Inorganic arsenic is methylated in the body by arsenic (III) methyltransferase (AS3MT). Arsenic methylation is thought to play a role in arsenic-related epigenetic phenomena, including aberrant DNA and histone methylation. However, it is unclear whether the promoter of the AS3MT gene, which codes for AS3MT, is differentially methylated as a function of arsenic exposure. In this study, we evaluated AS3MT promoter methylation according to exposure, assessed by urinary arsenic excretion in a stratified random sample of 48 participants from the Strong Heart Study who had urine arsenic measured at baseline and DNA available from 1989 to 1991 and 1998–1999. For this study, all data are from the 1989–1991 visit. We measured AS3MT promoter methylation at its 48 CpG loci by bisulphite sequencing. We compared mean  % methylation at each CpG locus by arsenic exposure group using linear regression adjusted for study centre, age and sex. A hypomethylated region in the AS3MT promoter was associated with higher arsenic exposure. In vitro, arsenic induced AS3MT promoter hypomethylation, and it increased AS3MT expression in human peripheral blood mononuclear cells. These findings may suggest that arsenic exposure influences the epigenetic regulation of a major arsenic metabolism gene.     

Association of oestrogen receptor alpha gene polymorphism with the angiographic extent of coronary artery disease.

AIMS: To investigate the association between sequence variants in the promoter region of the oestrogen receptor-alpha (ER-alpha) gene and the angiographic severity of coronary artery disease (CAD). METHODS AND RESULTS: We studied 503 subjects undergoing coronary angiography (mean age 63+/-12 years, 72% men, 28% women). Coronary artery disease extent was assessed by the number of: (1) major coronary vessels with >50% narrowing (NMCV); (2) coronary vessels with any narrowing (NCV); (3) narrowed coronary segments (NCS). The number of thymine and adenine dinucleotide repeats [(TA)(n)], 1174 base-pairs upstream exon 1, was determined by PCR. The median number of (TA)(n)(18) was used to categorize subjects into long, short and mixed allele genotypes. Poisson regression was used to analyse the association between genotypes and CAD extent, with age category (age #10877;55 vs >55), sex, risk factors and age at onset of CAD as covariates. In young subjects, (TA)(n)length had a significant effect on NCS (P=0.047) and a borderline significant effect on NCV (P=0.066). Young subjects homozygous for long alleles had higher NCV and NCS compared to those homozygous for short alleles (NCV 3.7+/-2.4 vs 2.4+/-1.8, NCS 4.4+/-2.7 vs 3.1+/-2.3, respectively, P#10877;0.034). CONCLUSION: The (TA)(n)length in the ER-alpha gene promoter region is associated with the angiographic severity of CAD in young patients.     

Cytogenetic studies in bone marrow transplant recipients

Summary Chromosome studies were performed in 24 patients who underwent allogeneic bone marrow transplantation (BMT) for severe aplastic anaemia (8), chronic myeloid leukemia (5 in chronic, 2 in accelerated phase and 1 in lymphoid blast crisis), acute myeloid leukemia (6), acute lymphoblastic leukemia in relapse (1) and Hodgkin's disease (1). Donor-cell type engraftment was demonstrated in 21 patients: in all 17 sex-mismatched transplants and — as demonstrated by reconstitution with Ph-negative cell populations — in 4 CML patients with a sex-matched donor. Recipient-type mitoses were seen in the bone marrow of 5 cases (1 SAA, 3 CML, 1 AML) after transplantation. They were only observed on one occasion in patients with SAA (4 of 25 on day 33) and AML (44 of 50 on day 14). Despite the continued demonstration of some Ph-positive mitoses in 3 patients with CML up to day 28, 323 and 451 after BMT, respectively, all surviving CML patients are still in complete haematological and clinical remission. So far the significance of these cytogenetically abnormal persisting host cells remains unknown. Present address: Roswell Park Memorial Institute, Department of Genetics and Endocrinology, 666 Elm Street, Buffalo, NY 14 222, USA     

Does Social Support Predict Pregnant Mothers’ Information Seeking Behaviors on an Educational Website?

We examine how social support (perceived support and support from a spouse, or committed partner) may influence pregnant women’s information seeking behaviors on a pregnancy website. We assess information seeking behavior among participants in a trial testing the effectiveness of a web-based intervention for appropriate gestational weight gain. Participants were pregnant women (N = 1,329) recruited from clinics and private practices in one county in the Northeast United States. We used logistic regression models to estimate the likelihood of viewing articles, blogs, frequently asked questions (FAQs), and resources on the website as a function of perceived social support, and support from a spouse or relationship partner. All models included socio-demographic controls (income, education, number of adults and children living at home, home Internet use, and race/ethnicity). Compared to single women, women who were married or in a committed relationship were more likely to information seek online by viewing articles (OR 1.95, 95 % CI [1.26–3.03]), FAQs (OR 1.64 [1.00–2.67]), and blogs (OR 1.88 [1.24–2.85]). Women who felt loved and valued (affective support) were more likely to seek information by viewing articles on the website (OR 1.19 [1.00–1.42]). While the Internet provides a space for people who have less social support to access health information, findings from this study suggest that for pregnant women, women who already had social support were most likely to seek information online. This finding has important implications for designing online systems and content to encourage pregnant women with fewer support resources to engage with content.     

Rationing Limited Healthcare Resources in the COVID-19 Era and Beyond: Ethical Considerations Regarding Older Adults

Coronavirus disease 2019 (COVID-19) continues to impact older adults disproportionately with respect to serious consequences ranging from severe illness and hospitalization to increased mortality risk. Concurrently, concerns about potential shortages of healthcare professionals and health supplies to address these issues have focused attention on how these resources are ultimately allocated and used. Some strategies, for example, misguidedly use age as an arbitrary criterion that disfavors older adults in resource allocation decisions. This is a companion article to the American Geriatrics Society (AGS) position statement, “Resource Allocation Strategies and Age-Related Considerations in the COVID-19 Era and Beyond.” It is intended to inform stakeholders including hospitals, health systems, and policymakers about ethical considerations that should be considered when developing strategies for allocation of scarce resources during an emergency involving older adults. This review presents the legal and ethical background for the position statement and discusses these issues that informed the development of the AGS positions: (1) age as a determining factor, (2) age as a tiebreaker, (3) criteria with a differential impact on older adults, (4) individual choices and advance directives, (5) racial/ethnic disparities and resource allocation, and (6) scoring systems and their impact on older adults. It also considers the role of advance directives as expressions of individual preferences in pandemics. J Am Geriatr Soc 68:1143–1149, 2020.     

Missing canines: a novel aetiology

Infant oral mutilation is the practice of removing developing tooth germs, commonly the mandibular canine, in infants up to the age of 1 year. Subsequent complications include missing, impacted or hypoplastic permanent anterior and canine teeth. We report on a case of bilaterally missing lower canines thought to be due to infant oral mutilation. It is important that general dental practitioners are aware of this practice and resulting complications when treating families from sub‐Saharan East Africa.     

Association of Global DNA Methylation and Global DNA Hydroxymethylation with Metals and Other Exposures in Human Blood DNA Samples

Background: The association between human blood DNA global methylation and global hydroxymethylation has not been evaluated in population-based studies. No studies have evaluated environmental determinants of global DNA hydroxymethylation, including exposure to metals.Objective: We evaluated the association between global DNA methylation and global DNA hydroxymethylation in 48 Strong Heart Study participants for which selected metals had been measured in urine at baseline and DNA was available from 1989–1991 (visit 1) and 1998–1999 (visit 3).Methods: We measured the percentage of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in samples using capture and detection antibodies followed by colorimetric quantification. We explored the association of participant characteristics (i.e., age, adiposity, smoking, and metal exposure) with both global DNA methylation and global DNA hydroxymethylation.Results: The Spearman’s correlation coefficient for 5-mC and 5-hmC levels was 0.32 (p = 0.03) at visit 1 and 0.54 (p < 0.001) at visit 3. Trends for both epigenetic modifications were consistent across potential determinants. In cross-sectional analyses, the odds ratios of methylated and hydroxymethylated DNA were 1.56 (95% CI: 0.95, 2.57) and 1.76 (95% CI: 1.07, 2.88), respectively, for the comparison of participants above and below the median percentage of dimethylarsinate. The corresponding odds ratios were 1.64 (95% CI: 1.02, 2.65) and 1.16 (95% CI: 0.70, 1.94), respectively, for the comparison of participants above and below the median cadmium level. Arsenic exposure and metabolism were consistently associated with both epigenetic markers in cross-sectional and prospective analyses. The positive correlation of 5-mC and 5-hmC levels was confirmed in an independent study population.Conclusions: Our findings support that both epigenetic measures are related at the population level. The consistent trends in the associations between these two epigenetic modifications and the characteristics evaluated, especially arsenic exposure and metabolism, suggest the need for understanding which of the two measures is a better biomarker for environmental epigenetic effects in future large-scale epidemiologic studies.Citation: Tellez-Plaza M, Tang WY, Shang Y, Umans JG, Francesconi KA, Goessler W, Ledesma M, Leon M, Laclaustra M, Pollak J, Guallar E, Cole SA, Fallin MD, Navas-Acien A. 2014. Association of global DNA methylation and global DNA hydroxymethylation with metals and other exposures in human blood DNA samples. Environ Health Perspect 122:946–954; http://dx.doi.org/10.1289/ehp.1306674     

Verwendung von Kuhmilch im Säuglingsalter

Background

There is a lack of valid studies to give evidence-based recommendations for the use of cow-milk in infancy. The Nutrition Committee on Nutrition of the ÖGKJ (Austrian Associaiton for Child and Adolescent Medicine) has reviewed the available data and provides a practical guideline in order to transform scientific knowledge into practice.

Practical guideline

Before the age of 6 months it is recommended that cow milk in infant nutrition be completely avoided. From the age of 6 months on, cow milk can be introduced, starting with small amounts of cow milk used for the preparation of complementary feeding consisting of cereals. During the second year of life the amount of cow milk can be slowly increased up to 100 ml/day diluted with water in a 1:1 ratio. Cow milk should be used for maximum of one complementary meal and cow milk should not be combined with meat. Cow milk is not to be used as a beverage in infancy.     

Annual Research Review: A meta-analytic review of worldwide suicide rates in adolescents

Suicide is a leading cause of death among youth worldwide. The purpose of the current review was to examine recent cross-national trends in suicide mortality rates among 10- to 19-year-olds. This study extracted suicide mortality data from the World Health Organization's (WHO) Mortality Database for the most recent year (since 2010) from any country with available high-quality data (as defined by the WHO's guidelines). Data on access to lethal means (firearms, railways) and measures of economic quality (World Bank Income Group) and inequality (Gini coefficients) were obtained from publicly available data sources. Cross-national suicide mortality rates in youth were heterogeneous. The pooled estimate across all ages, sexes, and countries was 3.77/100,000 people. The highest suicide rates were found in Estonia, New Zealand, and Uzbekistan. Suicide rates were higher among older compared with younger adolescents and higher among males than females. The most common suicide methods were hanging/suffocation and jumping/lying in front of a moving object or jumping from a height. Firearm and railway access were related to suicide deaths by firearms and jumping/lying, respectively. Economic quality and inequality were not related to overall suicide mortality rates. However, economic inequality was correlated with a higher ratio of male:female suicides. This study provides a recent update of cross-national suicide trends in adolescents. Findings replicate prior patterns related to age, sex, geographic region, and common suicide methods. New to this review are findings relating suicide method accessibility to suicide mortality rates and the significant association between income inequality and the ratio of male:female suicide. Future research directions include expanding the worldwide coverage to more low- and middle-income countries, examining demographic groupings beyond binary sex and to race/ethnicity within countries, and clarifying factors that account for cross-national differences in suicide trends.