Effect of prenatal DHA supplementation on the infant epigenome: results from a randomized controlled trial

BACKGROUND: Evidence is accumulating that nutritional exposures in utero can influence health outcomes in later life. Animal studies and human epidemiological studies have implicated epigenetic modifications as playing a key role in this process, but there are limited data from large well-controlled human intervention trials. This study utilized a large double-blind randomized placebo-controlled trial to test whether a defined nutritional exposure in utero, in this case docosahexaenoic acid (DHA), could alter the infant epigenome. Pregnant mothers consumed DHA-rich fish oil (800 mg DHA/day) or placebo supplements from 20 weeks' gestation to delivery. Blood spots were collected from the children at birth (n = 991) and blood leukocytes at 5 years (n = 667). Global DNA methylation was measured in all samples, and Illumina HumanMethylation450K BeadChip arrays were used for genome-wide methylation profiling in a subset of 369 children at birth and 65 children at 5 years. RESULTS: There were no differences in global DNA methylation levels between the DHA and control group either at birth or at 5 years, but we identified 21 differentially methylated regions (DMRs) at birth, showing small DNA methylation differences (<5%) between the treatment groups, some of which seemed to persist until 5 years. The number of DMRs at birth was greater in males (127 DMRs) and in females (72 DMRs) separately, indicating a gender-specific effect. CONCLUSION: Maternal DHA supplementation during the second half of pregnancy had small effects on DNA methylation of infants. While the potential functional significance of these changes remains to be determined, these findings further support the role of epigenetic modifications in developmental programming in humans and point the way for future studies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12605000569606 and ACTRN12611001127998.Susan J. van Dijk, Jing Zhou, Timothy J. Peters, Michael Buckley, Brodie Sutcliffe, Yalchin Oytam, Robert A. Gibson, Andrew McPhee, Lisa N. Yelland, Maria Makrides, Peter L. Molloy and Beverly S. Muhlhausle

Lumos: a statewide linkage programme in Australia integrating general practice data to guide system redesign

ObjectiveWith ageing of the Australian population, more people are living longer and experiencing chronic or complex health conditions. The challenge is to have information that supports the integration of services across the continuum of settings and providers, to deliver person-centred, seamless, efficient and effective healthcare. However, in Australia, data are typically siloed within health settings, precluding a comprehensive view of patient journeys. Here, we describe the establishment of the Lumos programme—the first statewide linked data asset across primary care and other settings in Australia and evaluate its representativeness to the census population.Methods and analysisRecords extracted from general practices throughout New South Wales (NSW), Australia’s most populous state, were linked to patient records from acute and other settings. Innovative privacy and security technologies were employed to facilitate ongoing and regular updates. The marginal demographic distributions of the Lumos cohort were compared with the NSW census population by calculating multiple measures of representation to evaluate its generalisability.ResultsThe first Lumos programme data extraction linked 1.3 million patients’ general practice records to other NSW health system data. This represented 16% of the NSW population. The demographic distribution of patients in Lumos was &gt;95% aligned to that of the NSW population in the calculated measures of representativeness.ConclusionThe Lumos programme delivers an enduring, regularly updated data resource, providing unique insights about statewide, cross-setting healthcare utilisation. General practice patients represented in the Lumos data asset are representative of the NSW population overall. Lumos data can reliably be used to identify at-risk regions and groups, to guide the planning and design of health services and to monitor their impact throughout NSW.</jats:sec

Berkeleian principles in ecological realism: An ontological analysis

The Gibsonian ecological psychology is a reaction to the dualistic elements in classical theories of perception and action and to their epistemological anti-realist implications. Gibson's was a systematic and comprehensive enterprise in establishing an alternative theoretical perspective complete with its own ontology-ecological realism. We share Gibson's evident recognition of the significance of ontology for the scientific perspective it underlies. Definitive aspects of ecological psychology, the theory of direct perception, rejection of processing and representation are constructed within the framework of ecological realism. The epistemological realism of ecological psychology is underpinned by this ontology. Ultimately, the validity of these aspects, and the scientific utility of the program of ecological psychology when considered as a whole, depend on the integrity of ecological realism. One crucial step in evaluating the merit of ecological realism is a thorough recognition of its nature as an ontology. We discuss evidence in relation to key tenets, that there exists a familial affinity between ecological realism and Berkeley's seminal idealist thesis

Degrees of freedom and motor planning in purposive movement

This paper presents empirical evidence suggesting that healthy humans can perform a two degree of freedom visuo-motor pursuit tracking task with the same response time delay as a one degree of freedom task. In contrast, the time delay of the response is influenced markedly by the nature of the motor synergy required to produce it. We suggest a conceptual account of this evidence based on adaptive model theory, which combines theories of intermittency from psychology and adaptive optimal control from engineering. The intermittent response planning stage has a fixed period. It possesses multiple optimal trajectory generators such that multiple degrees of freedom can be planned concurrently, without requiring an increase in the planning period. In tasks which require unfamiliar motor synergies, or are deemed to be incompatible, internal adaptive models representing movement dynamics are inaccurate. This means that the actual response which is produced will deviate from the one which is planned. For a given target-response discrepancy, corrective response trajectories of longer duration are planned, consistent with the principle of speed-accuracy trade-off. Compared to familiar or compatible tasks, this results in a longer response time delay and reduced accuracy. From the standpoint of the intermittency approach, the findings of this study help make possible a more integral and predictive account of purposive action. (c) 2005 Elsevier B.V. All rights reserved

Postural context alters the stability of bimanual coordination by modulating the crossed excitability of corticospinal pathways.

The tendency for movements of the upper limbs to be drawn systematically toward one another and to follow similar spatiotemporal trajectories is well known. Although suppression of this tendency is integral to tasks of daily living, its exploitation may prove to be critical in the rehabilitation of acquired hemiplegias. In general, however, the task-related factors that determine the degree of coupling between the upper limbs and the mechanisms that mediate bilateral interactions between neural pathways projecting to the muscles of the arm and hand are not yet well understood. We present evidence that the postural context in which human participants perform upper limb movements determines the relative stability of patterns of bimanual coordination. Manipulation of the axes of rotation of forearm movements reversed the relative stability of simultaneous and alternating patterns of bimanual coordination. Transcranial magnetic stimulation of motor cortex revealed that these manipulations of postural context altered the crossed modulation of excitability in corticospinal pathways that arises from movement of the opposite limb. Furthermore, modulation of responses to electrical stimulation of the cervicomedullary junction indicated that crossed modulation was also expressed at the level of the spinal motoneurons. Our data support the view that crossed modulation of excitability in corticospinal pathways mediates the stability of bimanual coordination. Furthermore, task-related factors that are sufficient to give rise to changes in the stability of bimanual coordination are accompanied by crossed modulation of excitability at multiple levels of the neuraxis, indicative of a failure of inhibitory control

Do preferred patterns of coordination in rhythmic multijoint arm movement result from optimal use of bifunctional muscles

We investigated coordination between rhythmic flexion-extension (FE) and supination-pronation (SP) movements at the elbow joint-complex using a 2-degrees of freedom motorized robot arm. Most participants spontaneously adopt an inphase coordination pattern (i.e. forearm supination is synchronized with elbow flexion) in this task. The goal of the present study was to assess whether this behaviour is due to patterns of efference that are optimized to exploit the biomechanical advantage bestowed by the bifunctional nature of the Biceps Brachii (BB) muscle, which acts to both flex the elbow and supinate the forearm. Electromyograms of BB and two other arm muscles were recorded during an experiment in which participants had to produce oscillatory FE and SP movements either in isolation or in combination (at a freely chosen phase relationship). In a normal (neutral) dynamic context, BB was more active during combined (in phase) FE and SP than when these movements were performed in isolation. The motorized robot arm was used to generate an alternative dynamic context which promoted the opposite (i.e., anti-phase) pattern of coordination. In these circumstances, however, the in-phase mode of coordination remained predominant. It is proposed that the synergistic relations between the muscles engaged in this task are not sufficiently flexible to permit exploitation of the bifunctional characteristic of BB in altered dynamical contexts

Surface coatings of ZnO nanoparticles mitigate differentially a host of transcriptional, protein and signalling responses in primary human olfactory cells

Background: Inhaled nanoparticles have been reported in some instances to translocate from the nostril to the olfactory bulb in exposed rats. In close proximity to the olfactory bulb is the olfactory mucosa, within which resides a niche of multipotent cells. Cells isolated from this area may provide a relevant in vitro system to investigate potential effects of workplace exposure to inhaled zinc oxide nanoparticles. Methods: Four types of commercially-available zinc oxide (ZnO) nanoparticles, two coated and two uncoated, were examined for their effects on primary human cells cultured from the olfactory mucosa. Human olfactory neurosphere-derived (hONS) cells from healthy adult donors were analyzed for modulation of cytokine levels, activation of intracellular signalling pathways, changes in gene-expression patterns across the whole genome, and compromised cellular function over a 24 h period following exposure to the nanoparticles suspended in cell culture medium. Results: ZnO nanoparticle toxicity in hONS cells was mediated through a battery of mechanisms largely related to cell stress, inflammatory response and apoptosis, but not activation of mechanisms that repair damaged DNA. Surface coatings on the ZnO nanoparticles mitigated these cellular responses to varying degrees. Conclusions: The results indicate that care should be taken in the workplace to minimize generation of, and exposure to, aerosols of uncoated ZnO nanoparticles, given the adverse responses reported here using multipotent cells derived from the olfactory mucosa