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.     

Homicide with a screwdriver and simulation of a similar offence by self-infliction of injuries

In an underground garage of a department store, a 52-year-old woman was attacked and fatally wounded by several stabs with a screwdriver. The offence happened as the woman was getting into her car. The homicide itself and the subsequent trial were extensively covered in the local media. A few days before the judgement was pronounced, another attack in an underground garage was reported to the police of the town, where the homicide had happened. A 52-year-old woman claimed to have been hurt by an assailant. The wound pattern (several equally shallow cuts arranged in groups), however, suggested self-infliction, which was finally admitted by the informant. The 'victim' used a newly bought kitchen knife to cut herself and left it at the place of the alleged assault. The knife blade was soiled with blood. Referring to the pertinent literature both cases are compared with regard to the injury characteristics and to the damage to the clothing. The morphological features of screwdriver injuries, the criteria differentiating self-infliction and assault as well as the manifestation of copycat offences are discussed.     

Metformin and Rapamycin Reduce Pancreatic Cancer Growth in Obese Prediabetic Mice by Distinct MicroRNA-Regulated Mechanisms

Metformin treatment is associated with a decreased risk and better prognosis of pancreatic cancer (PC) in patients with type 2 diabetes, but the mechanism of metformin’s PC growth inhibition in the context of a prediabetic state is unknown. We used a Panc02 pancreatic tumor cell transplant model in diet-induced obese (DIO) C57BL/6 mice to compare the effects of metformin and the direct mammalian target of rapamycin (mTOR) inhibitor rapamycin on PC growth, glucose regulation, mTOR pathway signaling, and candidate microRNA (miR) expression. In DIO/prediabetic mice, metformin and rapamycin significantly reduced pancreatic tumor growth and mTOR-related signaling. The rapamycin effects centered on decreased mTOR-regulated growth and survival signaling, including increased expression of let-7b and cell cycle–regulating miRs. Metformin (but not rapamycin) reduced glucose and insulin levels and expression of miR-34a and its direct targets Notch, Slug, and Snail. Metformin also reduced the number and size of Panc02 tumor spheres in vitro and inhibited the expression of Notch in spheroids. Our results suggest that metformin and rapamycin can both inhibit pancreatic tumor growth in obese, prediabetic mice through shared and distinct mechanisms. Metformin and direct mTOR inhibitors, alone or possibly in combination, represent promising intervention strategies for breaking the diabetes-PC link.     

Long hospitalization is the most important risk factor for early weaning from breast milk in premature babies

Aim: To identify certain variables related to the infants' course that might have an impact on the mothers' decision to breastfeed.
Patients and Method: Retrospective survey including all patients <1500 g birth weight (BW) treated between January 1, 2000 and December 31, 2005 at the Neonatal Intensive Care Unit of the Medical University of Vienna who were not transferred to another hospital. Multiple regression analysis of the following variables was carried out: gestational age (GA), BW, length of stay (LOS), parity, singleton or multiple gestation, sex and severe morbidity.
Results: Of the 239 patients included, 142 (60%) were fed breast milk at the time of final discharge, 97 (40%) were fed formula. LOS was significantly correlated with the probability of being breastfed: the shorter it was, the higher was the probability of being breastfed at the time of final discharge (p = 0.0064 for singletons, p = 0.001 for multiples). Lower GA also increased the probability of being breastfed, but this was only statistically significant for multiples (p = 0.001).
Conclusion: This study shows clearly that the most important influencing factor on the mothers' decision to continue breastfeeding is the LOS. Thus more emphasis should be put on encouraging mothers to continue lactation throughout their babies' hospital stay.