Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Salivary biomarkers of HPA axis and autonomic activity in adults with intellectual disability with and without stereotyped and self-injurious behavior disorders

Salivary levels of biomarkers for the hypothalamic–pituitary–adrenal axis (HPA; cortisol) and sympatho-adreno-medullary system (SAM; α-amylase) were measured in 51 adults (57% male) with neurodevelopmental disorders associated with intellectual disability (i.e., mental retardation) and chronic self-injurious behavior (SIB) and compared with matched controls without SIB. Cortisol levels differed significantly (p < 0.01) between the SIB and control group (SIB > control). Within-group analyses showed significant differences (p < 0.05) in levels of salivary α-amylase between individuals with SIB and those with SIB meeting criteria for stereotyped movement disorder (SMD; SIB + SMD > SIB). Salivary α-amylase was significantly correlated with frequency of stereotypy among the SIB group (r = 0.36, p < 0.05). These preliminary findings warrant further exploration into the role of the SAM system in the pathophysiology of SIB and related repetitive behaviors among individuals with neurodevelopmental disorders associated with intellectual disability

Theoretical modeling for the stereo mission

We summarize the theory and modeling efforts for the STEREO mission, which will be used to interpret the data of both the remote-sensing (SECCHI, SWAVES) and in-situ instruments (IMPACT, PLASTIC). The modeling includes the coronal plasma, in both open and closed magnetic structures, and the solar wind and its expansion outwards from the Sun, which defines the heliosphere. Particular emphasis is given to modeling of dynamic phenomena associated with the initiation and propagation of coronal mass ejections (CMEs). The modeling of the CME initiation includes magnetic shearing, kink instability, filament eruption, and magnetic reconnection in the flaring lower corona. The modeling of CME propagation entails interplanetary shocks, interplanetary particle beams, solar energetic particles (SEPs), geoeffective connections, and space weather. This review describes mostly existing models of groups that have committed their work to the STEREO mission, but is by no means exhaustive or comprehensive regarding alternative theoretical approaches

Visual Evoked Potentials Change as Heart Rate and Carotid Pressure Change

The relationship between cardiovascular activity and the brain was explored by recording visual evoked potentials from the occipital regions of the scalp during systolic and diastolic pressure (Experiment I) and during fast and slow heartbeats at systolic and diastolic pressure (Experiment II). Visual evoked potentials changed significantly as heart rate and carotid pressure fluctuated normally, and these changes were markedly different in the right and left cerebral hemispheres. Evoked potentials recorded from the right hemisphere during various cardiac events differed significantly, whereas those recorded from the left did not. In both experiments, differences in the right hemisphere were due primarily to the P1 component, which was larger at diastolic than at systolic pressure. The present findings are consistent with formulations from behavioral studies suggesting that baroreceptor activity can influence sensory intake, and suggest that hemispheric specialization may play an important role in the relationship between cardiac events, the brain and behavior.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73146/1/j.1469-8986.1982.tb02579.x.pd

Deciding Together?:Best Interests and Shared Decision-Making in Paediatric Intensive Care

In the western healthcare, shared decision making has become the orthodox approach to making healthcare choices as a way of promoting patient autonomy. Despite the fact that the autonomy paradigm is poorly suited to paediatric decision making, such an approach is enshrined in English common law. When reaching moral decisions, for instance when it is unclear whether treatment or non-treatment will serve a child’s best interests, shared decision making is particularly questionable because agreement does not ensure moral validity. With reference to current common law and focusing on intensive care practice, this paper investigates what claims shared decision making may have to legitimacy in a paediatric intensive care setting. Drawing on key texts, I suggest these identify advantages to parents and clinicians but not to the child who is the subject of the decision. Without evidence that shared decision making increases the quality of the decision that is being made, it appears that a focus on the shared nature of a decision does not cohere with the principle that the best interests of the child should remain paramount. In the face of significant pressures toward the displacement of the child’s interests in a shared decision, advantages of a shared decision to decisional quality require elucidation. Although a number of arguments of this nature may have potential, should no such advantages be demonstrable we have cause to revise our commitment to either shared decision making or the paramountcy of the child in these circumstances