Exposure to Moderate Air Pollution during Late Pregnancy and Cord Blood Cytokine Secretion in Healthy Neonates

Ambient air pollution can alter cytokine concentrations as shown in vitro and following short-term exposure to high air pollution levels in vivo. Exposure to pollution during late pregnancy has been shown to affect fetal lymphocytic immunophenotypes. However, effects of prenatal exposure to moderate levels of air pollutants on cytokine regulation in cord blood of healthy infants are unknown. In a birth cohort of 265 healthy term-born neonates, we assessed maternal exposure to particles with an aerodynamic diameter of 10 µm or less (PM₁₀), as well as to indoor air pollution during the last trimester, specifically the last 21, 14, 7, 3 and 1 days of pregnancy. As a proxy for traffic-related air pollution, we determined the distance of mothers' homes to major roads. We measured cytokine and chemokine levels (MCP-1, IL-6, IL-10, IL-1ß, TNF-α and GM-CSF) in cord blood serum using LUMINEX technology. Their association with pollution levels was assessed using regression analysis, adjusted for possible confounders. Mean (95%-CI) PM₁₀ exposure for the last 7 days of pregnancy was 18.3 (10.3-38.4 µg/m³). PM₁₀ exposure during the last 3 days of pregnancy was significantly associated with reduced IL-10 and during the last 3 months of pregnancy with increased IL-1ß levels in cord blood after adjustment for relevant confounders. Maternal smoking was associated with reduced IL-6 levels. For the other cytokines no association was found. Our results suggest that even naturally occurring prenatal exposure to moderate amounts of indoor and outdoor air pollution may lead to changes in cord blood cytokine levels in a population based cohort

The role of epigenetic dysregulation in the epidemic of allergic disease

The epidemic of allergic disease in early life is one of the clearest indicators that the developing immune system is vulnerable to modern environmental changes. A range of environmental exposures epidemiologically associated with allergic disease have been shown to have effects on the foetal immune function in pregnancy, including microbial burden, dietary changes and environmental pollutants. Preliminary studies now suggest that these early effects on immune development may be mediated epigenetically through a variety of processes that collectively modify gene expression and allergic susceptibility and that these effects are potentially heritable across generations. It is also possible that rising rates of maternal allergy, a recognised direct risk factor for infant allergic disease, may be further amplifying the effects of environmental changes. Whilst effective prevention strategies are the ultimate goal in reversing the allergy epidemic, the specific environmental drivers, target genes, and intracellular pathways and mechanisms of early life immune programming are still unclear. It is hoped that identifying genes that are differentially regulated in association with subsequent allergic disease will assist in identifying causal pathways and upstream contributing environmental factors. In this way, epigenetic paradigms are likely to provide valuable insights into how the early environment can be modified to more favourably drive immune development and reverse the allergic epidemic

Influence of Socioeconomic Status Trajectories on Innate Immune Responsiveness in Children

Lower socioeconomic status (SES) is consistently associated with poor health, yet little is known about the biological mechanisms underlying this inequality. In children, we examined the impact of early-life SES trajectories on the intensity of global innate immune activation, recognizing that excessive activation can be a precursor to inflammation and chronic disease.Stimulated interleukin-6 production, a measure of immune responsiveness, was analyzed ex vivo for 267 Canadian schoolchildren from a 1995 birth cohort in Manitoba, Canada. Childhood SES trajectories were determined from parent-reported housing data using a longitudinal latent-class modeling technique. Multivariate regression was conducted with adjustment for potential confounders.SES was inversely associated with innate immune responsiveness (p=0.003), with persistently low-SES children exhibiting responses more than twice as intense as their high-SES counterparts. Despite initially lower SES, responses from children experiencing increasing SES trajectories throughout childhood were indistinguishable from high-SES children. Low-SES effects were strongest among overweight children (p<0.01). Independent of SES trajectories, immune responsiveness was increased in First Nations children (p<0.05) and urban children with atopic asthma (p<0.01).These results implicate differential immune activation in the association between SES and clinical outcomes, and broadly imply that SES interventions during childhood could limit or reverse the damaging biological effects of exposure to poverty during the preschool years

Influence of Maternal Dysmetabolic Conditions During Pregnancy on Cardiovascular Disease

Pathogenic factors associated with maternal hypercholesterolemia, obesity, and diabetic conditions during pregnancy influence fetal development and predispose offspring to cardiovascular disease. Animal models have established cause–effect relationships consistent with epidemiological findings in humans and have demonstrated, in principle, that interventions before or during pregnancy can reduce or prevent pathogenic in utero programming. However, little is known about the mechanisms by which maternal dysmetabolic conditions enhance disease susceptibility in offspring. Identification of these mechanisms is rendered more difficult by the fact that programming effects in offspring may be latent and may require conventional risk factors and inherited genetic co-factors to become clinically manifest. Given the increasing prevalence of maternal risk factors, which is expected to lead to a wave of cardiovascular disease in the coming decades, and the length of prospective studies on developmental programming in humans, greater-than-usual emphasis on experimental models and translational studies is necessary

What Happened to Gray Whales during the Pleistocene? The Ecological Impact of Sea-Level Change on Benthic Feeding Areas in the North Pacific Ocean

Gray whales (Eschrichtius robustus) undertake long migrations, from Baja California to Alaska, to feed on seasonally productive benthos of the Bering and Chukchi seas. The invertebrates that form their primary prey are restricted to shallow water environments, but global sea-level changes during the Pleistocene eliminated or reduced this critical habitat multiple times. Because the fossil record of gray whales is coincident with the onset of Northern Hemisphere glaciation, gray whales survived these massive changes to their feeding habitat, but it is unclear how.We reconstructed gray whale carrying capacity fluctuations during the past 120,000 years by quantifying gray whale feeding habitat availability using bathymetric data for the North Pacific Ocean, constrained by their maximum diving depth. We calculated carrying capacity based on modern estimates of metabolic demand, prey availability, and feeding duration; we also constrained our estimates to reflect current population size and account for glaciated and non-glaciated areas in the North Pacific. Our results show that key feeding areas eliminated by sea-level lowstands were not replaced by commensurate areas. Our reconstructions show that such reductions affected carrying capacity, and harmonic means of these fluctuations do not differ dramatically from genetic estimates of carrying capacity.Assuming current carrying capacity estimates, Pleistocene glacial maxima may have created multiple, weak genetic bottlenecks, although the current temporal resolution of genetic datasets does not test for such signals. Our results do not, however, falsify molecular estimates of pre-whaling population size because those abundances would have been sufficient to survive the loss of major benthic feeding areas (i.e., the majority of the Bering Shelf) during glacial maxima. We propose that gray whales survived the disappearance of their primary feeding ground by employing generalist filter-feeding modes, similar to the resident gray whales found between northern Washington State and Vancouver Island

Patients’ Perspectives of Oral and Injectable Type 2 Diabetes Medicines, Their Body Weight and Medicine-Taking Behavior in the UK: A Systematic Review and Meta-Ethnography

From Springer Nature via Jisc Publications Router.Publication status: PublishedHistory: received 2018-06-21, epub 2018-08-17, ppub 2018-10AbstractThe aim of this review is to identify peoples’ perspectives of their glucose-lowering and anti-obesity drugs in relation to diabetes and weight control and to explore how these views affect medication adherence. Theoretical perspectives associated with medicine-taking behavior are also explored. The systematic review was based on a meta-ethnography of qualitative studies identified through a search of 12 medical and social science databases and subsequent citation searches. The quality of all studies was assessed. Sixteen studies were included with data from 360 UK individuals. No relevant studies were identified which focused on anti-obesity and non-insulin injectable drugs. The review revealed that the patients’ perspectives and emotional state were influenced by starting and/or changing to a new glucose-lowering medicine. These were also influenced by prior medication experience, disease perceptions and interactions with clinicians. Despite reports of positive experiences with and positive perceptions of medicines, and of participation in strategies to regain life control, medication non-adherence was common. Accepting glucose-lowering medicines impacted on the individual’s perception of lifestyle changes, and it was notable that weight loss was not perceived as a strategy to support diabetes management. Synthesis revealed that more than one theory is required to explain medicine-taking behavior. New insights into the underlying factors of poor adherence and the specific practical issues identified in this review can help in the development of patient-centered interventions.Funding: Diabetes UK

Endurance performance is influenced by perceptions of pain and temperature: Theory, applications and safety considerations.

Models of endurance performance now recognise input from the brain, including an athlete’s ability to cope with various non-pleasurable perceptions during exercise, such as pain and temperature. Exercise training can reduce perceptions of both pain and temperature over time, partly explaining why athletes generally have a higher pain tolerance, despite a similar pain threshold, compared with active controls. Several strategies with varying efficacy may ameliorate the perceptions of pain (e.g. acetaminophen, transcranial direct current stimulation and transcutaneous electrical stimulation) and temperature (e.g. menthol beverages, topical menthol products and other cooling strategies, especially those targeting the head) during exercise to improve athletic performance. This review describes both the theory and practical applications of these interventions in the endurance sport setting, as well as the potentially harmful health consequences of their use