In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver

Background: Maternal smoking is one of the most important modifiable risk factors for low birthweight, which is strongly associated with increased cardiometabolic disease risk in adulthood. Maternal smoking reduces the levels of the methyl donor vitamin B12 and is associated with altered DNA methylation at birth. Altered DNA methylation may be an important mechanism underlying increased disease susceptibility; however, the extent to which this can be induced in the developing fetus is unknown.

Methods: In this retrospective study, we measured concentrations of cobalt, vitamin B12, and mRNA transcripts encoding key enzymes in the 1-carbon cycle in 55 fetal human livers obtained from 11 to 21 weeks of gestation elective terminations and matched for gestation and maternal smoking. DNA methylation was measured at critical regions known to be susceptible to the in utero environment. Homocysteine concentrations were analyzed in plasma from 60 fetuses.

Results: In addition to identifying baseline sex differences, we found that maternal smoking was associated with sex-specific alterations of fetal liver vitamin B12, plasma homocysteine and expression of enzymes in the 1-carbon cycle in fetal liver. In the majority of the measured parameters which showed a sex difference, maternal smoking reduced the magnitude of that difference. Maternal smoking also altered DNA methylation at the imprinted gene IGF2 and the glucocorticoid receptor (GR/NR3C1).

Conclusions: Our unique data strengthen studies linking in utero exposures to altered DNA methylation by showing, for the first time, that such changes are present in fetal life and in a key metabolic target tissue, human fetal liver. Furthermore, these data propose a novel mechanism by which such changes are induced, namely through alterations in methyl donor availability and changes in 1-carbon metabolism.

Virgin Olive Oil: Losses of Antioxidant Polar Phenolic Compounds due to Storage, Packaging, and Culinary Uses

Virgin olive oil is a high quality natural product obtained only by physical means. In addition to triacylglycerols it contains nutritionally important polar and non-polar antioxidant phenols and other bioactive ingredients. The polar fraction is a complex mixture of phenolic acids, simple phenols, derivatives of the glycosides oleuropein and ligstroside, lignans, and flavonoids. These compounds contribute significantly to the stability, flavor, and biological value of virgin olive. In the various stages of production, during storage and in the culinary uses, polar phenols and other valuable bioactive ingredients may be damaged. Oxidation, photo-oxidation, enzymic hydrolysis and heating at frying temperatures have a serious adverse effect. Due to the biological importance of the oil and its unique character, analytical methods have been developed to evaluate antioxidant activity or analyse complex phenol mixtures. These are based on radical scavenging assays and chromatographic techniques. Hyphenated methods are also used including liquid chromatography-mass spectrometry and liquid chromatography-nuclear magnetic resonance spectroscopy.

Characterisation of UK and Irish Cold-Pressed Rapeseed Oils in Relation to Quality Indices and Constituents.

Cold-pressed rapeseed oil (CPRSO) is produced when seeds from an oilseed rape crop are mechanically crushed whilst at a low temperature. CPRSO’s popularity is rapidly expanding and is now produced in most Northern European countries including both N.Ireland and ROI. The CPRSO industry is still relatively new and therefore not as widely researched as other high quality oils. Fifteen CPRSO from The UK, Ireland and France were examined to determine characteristic differences between the oils. Two samples of extra-virgin olive oil and two samples of refined rapeseed oil were also included in the investigation to assess performance against market competitors. The antioxidant potential of the oils was assessed using the ABTS and DPPH radical scavenging assays. Both unexpectedly showed that refined rapeseed oil had the highest potential whilst there was significant difference between many of the CPRSO’s. The acid value (ACOS method Cd 3d-63) ranged widely from 0.47-3.41. To predict the stability during storage, an accelerated oxidation test was carried out where the oils were placed in an oven (60°C) and peroxide value was monitored. The results showed extra-virgin olive oil underwent the least oxidation during the trial. The refined rapeseed oil suffered the worst levels of oxidation whilst the CPRSO’s performed similarly but with some variation. Fatty acid composition was investigated with GC-MS and some of the major fatty acids were found to differ significantly between producers. Minor compound analysis was achieved with extraction and identification through HPLC. All results are critically discussed and compared to relevant published studies.

The application of Raman and anti-stokes Raman spectroscopy for in situ monitoring of structural changes in laser irradiated titanium dioxide materials

The use of Raman and anti-stokes Raman spectroscopy to investigate the effect of exposure to high power laser radiation on the crystalline phases of TiO₂ has been investigated. Measurement of the changes, over several time integrals, in the Raman and anti-stokes Raman of TiO₂ spectra with exposure to laser radiation is reported. Raman and anti-stokes Raman provide detail on both the structure and the kinetic process of changes in crystalline phases in the titania material. The effect of laser exposure resulted in the generation of increasing amounts of the rutile crystalline phase from the anatase crystalline phase during exposure. The Raman spectra displayed bands at 144 cm^-1 (A1g), 197 cm^-1 (Eg), 398 cm^-1 (B1g), 515 cm^-1 (A1g), and 640 cm^-1 (Eg) assigned to anatase which were replaced by bands at 143 cm^-1 (B1g), 235 cm^-1 (2 phonon process), 448 cm^-1 (Eg) and 612 cm^-1 (A1g) which were assigned to rutile. This indicated that laser irradiation of TiO₂ changes the crystalline phase from anatase to rutile. Raman and anti-stokes Raman are highly sensitive to the crystalline forms of TiO₂ and allow characterisation of the effect of laser irradiation upon TiO₂. This technique would also be applicable as an in situ method for monitoring changes during the laser irradiation process

Conduit artery structure and function in lowlanders and native highlanders: relationships with oxidative stress and role of sympathoexcitation

Research detailing the normal vascular adaptions to high altitude is minimal and often confounded by pathology (e.g. chronic mountain sickness) and methodological issues. We examined vascular function and structure in: (1) healthy lowlanders during acute hypoxia and prolonged (∼2 weeks) exposure to high altitude, and (2) high-altitude natives at 5050 m (highlanders). In 12 healthy lowlanders (aged 32 ± 7 years) and 12 highlanders (Sherpa; 33 ± 14 years) we assessed brachial endothelium-dependent flow-mediated dilatation (FMD), endothelium-independent dilatation (via glyceryl trinitrate; GTN), common carotid intima–media thickness (CIMT) and diameter (ultrasound), and arterial stiffness via pulse wave velocity (PWV; applanation tonometry). Cephalic venous biomarkers of free radical-mediated lipid peroxidation (lipid hydroperoxides, LOOH), nitrite (NO₂^–) and lipid soluble antioxidants were also obtained at rest. In lowlanders, measurements were performed at sea level (334 m) and between days 3–4 (acute high altitude) and 12–14 (chronic high altitude) following arrival to 5050 m. Highlanders were assessed once at 5050 m. Compared with sea level, acute high altitude reduced lowlanders’ FMD (7.9 ± 0.4 vs. 6.8 ± 0.4%; P = 0.004) and GTN-induced dilatation (16.6 ± 0.9 vs. 14.5 ± 0.8%; P = 0.006), and raised central PWV (6.0 ± 0.2vs. 6.6 ± 0.3 m s⁻¹; P = 0.001). These changes persisted at days 12–14, and after allometrically scaling FMD to adjust for altered baseline diameter. Compared to lowlanders at sea level and high altitude, highlanders had a lower carotid wall:lumen ratio (∼19%, P ≤ 0.04), attributable to a narrower CIMT and wider lumen. Although both LOOH and NO₂^– increased with high altitude in lowlanders, only LOOH correlated with the reduction in GTN-induced dilatation evident during acute (n = 11, r = −0.53) and chronic (n = 7, r = −0.69; P ≤ 0.01) exposure to 5050 m. In a follow-up, placebo-controlled experiment (n = 11 healthy lowlanders) conducted in a normobaric hypoxic chamber (inspired O₂ fraction () = 0.11; 6 h), a sustained reduction in FMD was evident within 1 h of hypoxic exposure when compared to normoxic baseline (5.7 ± 1.6 vs. 8.0 ±1.3%; P < 0.01); this decline in FMD was largely reversed following α₁-adrenoreceptor blockade. In conclusion, high-altitude exposure in lowlanders caused persistent impairment in vascular function, which was mediated partially via oxidative stress and sympathoexcitation. Although a lifetime of high-altitude exposure neither intensifies nor attenuates the impairments seen with short-term exposure, chronic high-altitude exposure appears to be associated with arterial remodelling.

Caught in a 'spiral': barriers to healthy eating and dietary health promotion needs from the perspective of unemployed young people and their service providers

The number of young people in Europe who are not in education, employment or training (NEET) is increasing. Given that young people from disadvantaged backgrounds tend to have diets of poor nutritional quality, this exploratory study sought to understand barriers and facilitators to healthy eating and dietary health promotion needs of unemployed young people aged 16-20 years. Three focus group discussions were held with young people (n=14). Six individual interviews and one paired interview with service providers (n=7). Data were recorded, transcribed verbatim and thematically content analysed. Themes were then fitted to social cognitive theory (SCT). Despite understanding of the principles of healthy eating, a ‘spiral’ of interrelated social, economic and associated psychological problems was perceived to render food and health of little value and low priority for the young people. The story related by the young people and corroborated by the service providers was of a lack of personal and vicarious experience with food. External, environmental factors such as the proliferation and proximity of fast food outlets and the high perceived cost of ‘healthy’ compared to ‘junk’ food rendered the young people low in self-efficacy and perceived control to make healthier food choices. Agency was instead expressed through consumption of junk food and substance abuse. Both the young people and service providers agreed that for dietary health promotion efforts to succeed, social problems needed addressed and agency encouraged through (individual and collective) active engagement of the young people themselves.

Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia

BACKGROUND: Exposure to environmental toxins during embryonic development may lead to epigenetic changes that influence disease risk in later life. Aflatoxin is a contaminant of staple foods in sub-Saharan Africa, is a known human liver carcinogen and has been associated with stunting in infants.

METHODS: We have measured aflatoxin exposure in 115 pregnant women in The Gambia and examined the DNA methylation status of white blood cells from their infants at 2-8 months old (mean 3.6 ± 0.9). Aflatoxin exposure in women was assessed using an ELISA method to measure aflatoxin albumin (AF-alb) adducts in plasma taken at 1-16 weeks of pregnancy. Genome-wide DNA methylation of infant white blood cells was measured using the Illumina Infinium HumanMethylation450beadchip.

RESULTS: AF-alb levels ranged from 3.9 to 458.4 pg/mg albumin. We found that aflatoxin exposure in the mothers was associated to DNA methylation in their infants for 71 CpG sites (false discovery rate < 0.05), with an average effect size of 1.7% change in methylation. Aflatoxin-associated differential methylation was observed in growth factor genes such as FGF12 and IGF1, and immune-related genes such as CCL28, TLR2 and TGFBI. Moreover, one aflatoxin-associated methylation region (corresponding to the miR-4520b locus) was identified.

CONCLUSIONS: This study shows that maternal exposure to aflatoxin during the early stages of pregnancy is associated with differential DNA methylation patterns of infants, including in genes related to growth and immune function. This reinforces the need for interventions to reduce aflatoxin exposure, especially during critical periods of fetal and infant development.

Plasmid DNA damage following exposure to atmospheric pressure non-thermal plasma: kinetics and influence of oxygen admixture

The nature and kinetics of plasmid DNA damage after DNA exposure to a kHz-driven atmospheric pressure nonthermal plasma jet has been investigated. Both single-strand break (SSB) and double-strand break (DSB) processes are reported here. While SSB had a higher rate constant, DSB is recognized to be more significant in living systems, often resulting in loss of viability. In a helium-operated plasma jet, adding oxygen to the feed gas resulted in higher rates of DNA DSB, which increased linearly with increasing oxygen content, up to an optimum level of 0.75% oxygen, after which the DSB rate decreased slightly, indicating an essential role for reactive oxygen species in the rapid degradation of DNA.

Nuclear disasters and health: lessons learned, challenges, and proposals

Past nuclear disasters, such as the atomic bombings in 1945 and major accidents at nuclear power plants, have highlighted similarities in potential public health effects of radiation in both circumstances, including health issues unrelated to radiation exposure. Although the rarity of nuclear disasters limits opportunities to undertake rigorous research of evidence-based interventions and strategies, identification of lessons learned and development of an effective plan to protect the public, minimise negative effects, and protect emergency workers from exposure to high-dose radiation is important. Additionally, research is needed to help decision makers to avoid premature deaths among patients already in hospitals and other vulnerable groups during evacuation. Since nuclear disasters can affect hundreds of thousands of people, a substantial number of people are at risk of physical and mental harm in each disaster. During the recovery period after a nuclear disaster, physicians might need to screen for psychological burdens and provide general physical and mental health care for many affected residents who might experience long-term displacement. Reliable communication of personalised risks has emerged as a challenge for health-care professionals beyond the need to explain radiation protection. To overcome difficulties of risk communication and provide decision aids to protect workers, vulnerable people, and residents after a nuclear disaster, physicians should receive training in nuclear disaster response. This training should include evidence-based interventions, support decisions to balance potential harms and benefits, and take account of scientific uncertainty in provision of community health care. An open and joint learning process is essential to prepare for, and minimise the effects of, future nuclear disasters.

Local conductance: A means to extract polarization and depolarizing fields near domain walls in ferroelectrics

Conducting atomic force microscopy images of bulk semiconducting BaTiO3 surfaces show clear stripe domain contrast. High local conductance correlates with strong out-of-plane polarization (mapped independently using piezoresponse force microscopy), and current- voltage characteristics are consistent with dipole-induced alterations in Schottky barriers at the metallic tip-ferroelectric interface. Indeed, analyzing current-voltage data in terms of established Schottky barrier models allows relative variations in the surface polarization, and hence the local domain structure, to be determined. Fitting also reveals the signature of surface-related depolarizing fields concentrated near domain walls. Domain information obtained from mapping local conductance appears to be more surface-sensitive than that from piezoresponse force microscopy. In the right materials systems, local current mapping could therefore represent a useful complementary technique for evaluating polarization and local electric fields with nanoscale resolution.

Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

Exposure to children and risk of active trachoma in Tanzanian women

The authors surveyed the trachoma status of 515 women aged 18-60 years and 527 children aged 1-7 years in the trachoma hyperendemic region of Kongwa, Tanzania, in 1989 to further describe the importance of exposure to young children as a risk factor for active trachoma in women. The women were identified as caretakers, who currently cared for children aged 1-7 years; noncaretakers, who lived with, but did not care for, children aged 1-7; or those without children aged 1-7 in the household. The age-adjusted odds ratios for active trachoma seemed to rise with greater exposure to young children, from 1.00 for women without such children, to 1.63 for noncaretakers and 2.43 for caretakers (trend test, p = 0.08). Among those who lived in households with young children, the prevalence of active trachoma in women increased with the total number of young children cared for and with the number of infected children cared for. The prevalence of active trachoma was 40% (6 of 15) for caretakers of three or more infected children, compared with 0 (0 of 88) for caretakers with no infected children (p < 0.0001). Caring for infected children also appeared to be associated with signs of chronic trachoma in caretakers. Noncaretakers who lived with infected children were not at a significantly increased risk for trachoma compared with noncaretakers who were not exposed to such children (5.4% (three of 56) vs. 5.6% (one of 18); p > 0.4). None of the facial signs observed in the children (flies on the face, nasal discharge, etc.) appeared to increase the odds ratio of active trachoma in caretakers beyond the increase associated with trachoma alone in the child. These data support the hypothesis that active disease in women is associated with direct caretaking of young children with active disease. Strategies that interrupt household transmission may affect the binding sequelae of trachoma in women.