Evaluating effects of aromatherapy massage on sleep in children with autism: a pilot study

Previous studies have found beneficial effects of aromatherapy massage for agitation in people with dementia, for pain relief and for poor sleep. Children with autism often have sleep difficulties, and it was thought that aromatherapy massage might enable more rapid sleep onset, less sleep disruption and longer sleep duration. Twelve children with autism and learning difficulties (2 girls and 10 boys aged between 12 years 2 months to 15 years 7 months) in a residential school participated in a within subjects repeated measures design: 3 nights when the children were given aromatherapy massage with lavender oil were compared with 14 nights when it was not given. The children were checked every 30 min throughout the night to determine the time taken for the children to settle to sleep, the number of awakenings and the sleep duration. One boy's data were not analyzed owing to lengthy absence. Repeated measures analysis revealed no differences in any of the sleep measures between the nights when the children were given aromatherapy massage and nights when the children were not given aromatherapy massage. The results suggest that the use of aromatherapy massage with lavender oil has no beneficial effect on the sleep patterns of children with autism attending a residential school. It is possible that there are greater effects in the home environment or with longer-term interventions.

Maternal psychosocial adversity and the longitudinal development of infant sleep

Research has identified associations between indicators of social disadvantage and the presence of child sleep problems. We examined the longitudinal development of infant sleep in families experiencing high (n = 58) or low (n = 64) levels of psychosocial adversity, and the contributions of neonatal self-regulatory capacities and maternal settling strategies to this development. Assessments of infant sleep at 4-, 7-, and 12-weeks postpartum indicated no differences in sleeping difficulties between high- and low-adversity groups. However, more infant sleep difficulties were reported in the high- versus low-adversity groups at 12- and 18-month follow-ups. Neonatal self-regulatory capacities were not related to the presence or absence of adversity, or to subsequent infant sleep quality. However, there were group differences in maternal settling strategies that did predict subsequent infant sleep difficulties. The pattern of sleep disturbance observed in association with maternal psychosocial adversity at 18-months was consistent with risk for broader impairments in child functioning.

Chronic hypoxia in the human neuroblastoma SH-SY5Y causes reduced expression of the putative alpha-secretases, ADAM10 and TACE, without altering their mRNA levels

Alzheimer's disease is more frequent following an ischemic or hypoxic episode, with levels of beta-amyloid peptides elevated in brains from patients. Similar increases are found after experimental ischemia in animals. It is possible that increased beta-amyloid deposition arises from alterations in amyloid precursor protein (APP) metabolism, indeed, we have shown that exposing cells of neuronal origin to chronic hypoxia decreased the secretion of soluble APP (sAPPalpha) derived by action of alpha-secretase on APP, coinciding with a decrease in protein levels of ADAM10, a disintegrin metalloprotease which is thought to be the major alpha-secretase. In the current study, we extended those observations to determine whether the expression of ADAM10 and another putative alpha-secretase, TACE, as well as the beta-secretase, BACE1 were regulated by chronic hypoxia at the level of protein and mRNA. Using Western blotting and RT-PCR, we demonstrate that after 48 h chronic hypoxia, such that sAPPalpha secretion is decreased by over 50%, protein levels of ADAM10 and TACE and by approximately 60% and 40% respectively with no significant decrease in BACE1 levels. In contrast, no change in the expression of the mRNA for these proteins could be detected. Thus, we conclude that under CH the level of the putative alpha-secretases, ADAM10 and TACE are regulated by post-translational mechanisms, most probably proteolysis, rather than at the level of transcription.

Ornamental Mediterranean plants in the UK: root adaptations to hypoxia and anoxia

Mediterranean species are popular landscape plants in the UK and well suited to the predicted climate change scenarios of hotter, drier summers. What is less clear is how these species will respond to the more unpredictable rainfall patterns also anticipated, where soil water-logging may become more prevalent, especially in urban environments where soil sealing can restrict drainage. Pot experiments on flooding of four Mediterranean species (Cistus × hybridus, Lavandula angustifolia ‘Munstead’, Salvia officinalis and Stachys byzantina) showed that the effects of waterlogging were only severe when the temperature was high and flooding prolonged. All plants survived the flooding in winter, but during the summer a 17-day flood resulted in the death of 30-40% of the Salvia officinalis and Cistus × hybridus. To examine the response of roots to oxygen deprivation over a range of conditions from total absence of oxygen (anoxia), low oxygen (hypoxia) and full aeration, rooted cuttings of Salvia officinalis were grown in a hydroponic-based system and mixtures of oxygen and nitrogen gases bubbled through the media. Anoxia was found to reduce root development dramatically. When the plants were subjected to a period of hypoxia they responded by increasing the production of lateral roots close to the surface thus enabling them to acclimate to subsequent anoxia. This greatly increased their chances of survival.

Evidence that convergence rather than accommodation controls intermittent distance exotropia

Purpose. This study considered whether vergence drives accommodation or accommodation drives vergence during the control of distance exotropia for near fixation. High accommodative convergence to accommodation (AC/A) ratios are often used to explain this control, but the role of convergence to drive accommodation (the CA/C relationship) is rarely considered. Atypical CA/C characteristics could equally, or better, explain common clinical findings. Methods. 19 distance exotropes, aged 4-11 years, were compared while controlling their deviation with 27 non-exotropic controls aged 5-9 years. Simultaneous vergence and accommodation responses were measured to a range of targets incorporating different combinations of blur, disparity and looming cues at four fixation distances between 2m and 33cm. Stimulus and response AC/A and CA/C ratios were calculated. Results. Accommodation responses for near targets (p=0.017) response gains (p=0.026) were greater in the exotropes than the controls. Despite higher clinical stimulus AC/A ratios, the distance exotropes showed lower laboratory response AC/A ratios (p=0.02), but significantly higher CA/C ratios (p=0.02). All the exotropes, whether the angle changed most with lenses (“controlled by accommodation”) or on occlusion (“controlled by fusion”), used binocular disparity not blur as their main cue to target distance. Conclusions. Increased vergence demand to control intermittent distance exotropia for near also drives significantly more accommodation. Minus lens therapy is more likely to act by correcting over-accommodation driven by controlling convergence, rather than by inducing blur-driven vergence. The use of convergence as a major drive to accommodation explains many clinical characteristics of distance exotropia, including apparently high near stimulus AC/A ratios.

Intermittent Escherichia coli O157:H7 colonisation at the terminal rectum mucosa of conventionally-reared lambs

In cattle, the lymphoid rich regions of the rectal-anal mucosa at the terminal rectum are the preferred site for Escherichia coli O157:H7 colonisation. All cattle infected by rectal swab administration demonstrate long-term E. coli O157:H7 colonisation, whereas orally challenged cattle do not demonstrate long-term E. coli O157:H7 colonisation in all animals. Oral, but not rectal challenge of sheep with E. coli O157:H7 has been reported, but an exact site for colonisation in sheep is unknown. To determine if E. coli O157:H7 can effectively colonise the ovine terminal rectum, in vitro organ culture (IVOC) was initiated. Albeit sparsely, large, densely packed E. coli O157:H7 micro-colonies were observed on the mucosa of ovine and control bovine terminal rectum explants. After necropsy of orally inoculated lambs, bacterial enumeration of the proximal and distal gastrointestinal tract did suggest a preference for E. coli O157:H7 colonisation at the ovine terminal rectum, albeit for both lymphoid rich and non-lymphoid sites. As reported for cattle, rectal inoculation studies were then conducted to determine if all lambs would demonstrate persistent colonisation at the terminal rectum. After necropsy of E. coli O157:H7 rectally inoculated lambs, most animals were not colonised at gastrointestinal sites proximal to the rectum, however, large densely packed micro-colonies of E. coli O157:H7 were observed on the ovine terminal rectum mucosa. Nevertheless, at the end point of the study (day 14), only one lamb had E. coli O157:H7 micro-colonies associated with the terminal rectum mucosa. A comparison of E. coli O157:H7 shedding yielded a similar pattern of persistence between rectally and orally inoculated lambs. The inability of E. coli O157:H7 to effectively colonise the terminal rectum mucosa of all rectally inoculated sheep in the long term, suggests that E. coli O157:H7 may colonise this site, but less effectively than reported previously for cattle.

Hypoxia and neurodegeneration

Periods of chronic hypoxia, which can arise from numerous cardiorespiratory disorders, predispose individuals to the development of dementias, particularly Alzheimer's disease (AD). AD is characterized in part by the increased production of amyloid beta peptide (Abeta), which forms the extracellular plaques by which the disease can be identified post mortem. Numerous studies have now shown that hypoxia, even in vitro, can increase production of Abeta in different cell types. Evidence has been produced to indicate hypoxia alters both expression of the Abeta precursor, APP, and also the expression of the secretase enzymes, which cleave Abeta from APP. Other studies implicate reduced Abeta degradation as a possible means by which hypoxia increases Abeta levels. Such variability may be attributable to cell-specific responses to hypoxia. Further evidence indicates that some, but not all of the cellular adaptations to chronic hypoxia (including alteration of Ca(2+) homeostasis) require Abeta formation. However, other aspects of hypoxic remodeling of cell function appear to occur independently of this process. The molecular and cellular responses to hypoxia contribute to our understanding of the clinical association of hypoxia and increased incidence of AD. However, it remains to be determined whether inhibition of one or more of the effects of hypoxia may be of benefit in arresting the development of this neurodegenerative disease.

Hypoxia suppresses astrocyte glutamate transport independently of amyloid formation

Sustained hypoxia alters the expression of numerous proteins and predisposes individuals to Alzheimer's disease (AD). We have previously shown that hypoxia in vitro alters Ca2+ homeostasis in astrocytes and promotes increased production of amyloid beta peptides (Abeta) of AD. Indeed, alteration of Ca2+ homeostasis requires amyloid formation. Here, we show that electrogenic glutamate uptake by astrocytes is suppressed by hypoxia (1% O2, 24h) in a manner that is independent of amyloid beta peptide formation. Thus, hypoxic suppression of glutamate uptake and expression levels of glutamate transporter proteins EAAT1 and EAAT2 were not mimicked by exogenous application of amyloid beta peptide, or by prevention of endogenous amyloid peptide formation (using inhibitors of either beta or gamma secretase). Thus, dysfunction in glutamate homeostasis in hypoxic conditions is independent of Abeta production, but will likely contribute to neuronal damage and death associated with AD following hypoxic events.

Hypoxia suppresses glutamate transport in astrocytes

Glutamate uptake by astrocytes is fundamentally important in the regulation of CNS function. Disruption of uptake can lead to excitotoxicity and is implicated in various neurodegenerative processes as well as a consequence of hypoxic/ischemic events. Here, we investigate the effect of hypoxia on activity and expression of the key glutamate transporters excitatory amino acid transporter 1 (EAAT1) [GLAST (glutamate-aspartate transporter)] and EAAT2 [GLT-1 (glutamate transporter 1)]. Electrogenic, Na+-dependent glutamate uptake was monitored via whole-cell patch-clamp recordings from cortical astrocytes. Under hypoxic conditions (2.5 and 1% O2 exposure for 24 h), glutamate uptake was significantly reduced, and pharmacological separation of uptake transporter subtypes suggested that the EAAT2 subtype was preferentially reduced relative to the EAAT1. This suppression was confirmed at the level of EAAT protein expression (via Western blots) and mRNA levels (via real-time PCR). These effects of hypoxia to inhibit glutamate uptake current and EAAT protein levels were not replicated by desferrioxamine, cobalt, FG0041, or FG4496, agents known to mimic effects of hypoxia mediated via the transcriptional regulator, hypoxia-inducible factor (HIF). Furthermore, the effects of hypoxia were not prevented by topotecan, which prevents HIF accumulation. In stark contrast, inhibition of nuclear factor-kappaB (NF-kappaB) with SN50 fully prevented the effects of hypoxia on glutamate uptake and EAAT expression. Our results indicate that prolonged hypoxia can suppress glutamate uptake in astrocytes and that this effect requires activation of NF-kappaB but not of HIF. Suppression of glutamate uptake via this mechanism may be an important contributory factor in hypoxic/ischemic triggered glutamate excitotoxicity.

Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation

CONTEXT: The link between long-haul air travel and venous thromboembolism is the subject of continuing debate. It remains unclear whether the reduced cabin pressure and oxygen tension in the airplane cabin create an increased risk compared with seated immobility at ground level. OBJECTIVE: To determine whether hypobaric hypoxia, which may be encountered during air travel, activates hemostasis. DESIGN, SETTING, AND PARTICIPANTS: A single-blind, crossover study, performed in a hypobaric chamber, to assess the effect of an 8-hour seated exposure to hypobaric hypoxia on hemostasis in 73 healthy volunteers, which was conducted in the United Kingdom from September 2003 to November 2005. Participants were screened for factor V Leiden G1691A and prothrombin G20210A mutation and were excluded if they tested positive. Blood was drawn before and after exposure to assess activation of hemostasis. INTERVENTIONS: Individuals were exposed alternately (> or =1 week apart) to hypobaric hypoxia, similar to the conditions of reduced cabin pressure during commercial air travel (equivalent to atmospheric pressure at an altitude of 2438 m), and normobaric normoxia (control condition; equivalent to atmospheric conditions at ground level, circa 70 m above sea level). MAIN OUTCOME MEASURES: Comparative changes in markers of coagulation activation, fibrinolysis, platelet activation, and endothelial cell activation. RESULTS: Changes were observed in some hemostatic markers during the normobaric exposure, attributed to prolonged sitting and circadian variation. However, there were no significant differences between the changes in the hypobaric and the normobaric exposures. For example, the median difference in change between the hypobaric and normobaric exposure was 0 ng/mL for thrombin-antithrombin complex (95% CI, -0.30 to 0.30 ng/mL); -0.02 [corrected] nmol/L for prothrombin fragment 1 + 2 (95% CI, -0.03 to 0.01 nmol/L); 1.38 ng/mL for D-dimer (95% CI, -3.63 to 9.72 ng/mL); and -2.00% for endogenous thrombin potential (95% CI, -4.00% to 1.00%). CONCLUSION: Our findings do not support the hypothesis that hypobaric hypoxia, of the degree that might be encountered during long-haul air travel, is associated with prothrombotic alterations in the hemostatic system in healthy individuals at low risk of venous thromboembolism.

A dynamical systems framework for intermittent data assimilation

We consider the problem of discrete time filtering (intermittent data assimilation) for differential equation models and discuss methods for its numerical approximation. The focus is on methods based on ensemble/particle techniques and on the ensemble Kalman filter technique in particular. We summarize as well as extend recent work on continuous ensemble Kalman filter formulations, which provide a concise dynamical systems formulation of the combined dynamics-assimilation problem. Possible extensions to fully nonlinear ensemble/particle based filters are also outlined using the framework of optimal transportation theory.

The relationship between parent and child dysfunctional beliefs about sleep and child sleep

Cognitive theories emphasise the role of dysfunctional beliefs about sleep in the development and maintenance of sleep-related problems (SRPs). The present research examines how parents' dysfunctional beliefs about children's sleep and child dysfunctional beliefs about sleep are related to each other and to children's subjective and objective sleep. Participants were 45 children aged 11 -12 years and their parents. Self-report measures of dysfunctional beliefs about sleep and child sleep were completed by children, mothers and fathers. Objective measures of child sleep were taken using actigraphy. The results showed that child dysfunctional beliefs about sleep were correlated with father (r=.43, p<.05) and mother (r=.43, p<.05) reported child SRPs, and with Sleep Onset Latency (r=.34, p<.05). Maternal dysfunctional beliefs about child sleep were related to child SRPs as reported by mothers (r=.44, p<.05), and to child dysfunctional beliefs about sleep (r=.37, p<.05). Some initial evidence was found for a mediation pathway in which child dyfunctional beliefs mediate the relationship between parent dysfunctional beliefs and child sleep. The results support the cognitive model of SRPs and contribute to the literature by providing the first evidence of familial aggregation of dysfunctional beliefs about sleep.

Molecular forms of porphobilinogen deaminase in acute intermittent porphyria. A study by Western immunoblotting

Acute intermittent porphyria is an inborn error of haem synthesis which is transmitted as a dominant character with variable phenotypic expression. The disorder is caused by a partial deficiency of porphobilinogen deaminase in all tissues so far studied. The nature of the enzymatic deficiency of porphobilinogen deaminase in haemolysates from patients with acute intermittent porphyria was examined by the use of monospecific antibody probes. In affected heterozygotes from three British pedigrees of diverse ancestry, the catalytic deficiency of porphobilinogen deaminase was accompanied by diminished enzyme protein, as determined by radial immunodiffusion. No evidence of functionally attenuated enzyme was demonstrable by kinetic studies. The molecular forms of the residual enzyme were investigated in red cell extracts and in lysed preparations of reticulocytes by a sensitive Western blotting procedure. This revealed the presence of reduced amounts of porphobilinogen deaminase polypeptide co-migrating with wild type enzyme (Mr approximately 40,000), and no evidence of variant forms in situ. The studies show that porphobilinogen deaminase deficiency in acute intermittent porphyria is commonly associated with a CRM-phenotype. The residual activity under these circumstances is thus related to expression of a single normal allele, since sensitive techniques detected neither aberrant nor degraded forms of the enzyme in erythroid tissues.

A longitudinal study of child sleep in high and low risk families: relationship to early maternal settling strategies and child psychological functioning

Objectives To investigate whether sleep disturbances previously found to characterise high risk infants: (a) persist into childhood; (b) are influenced by early maternal settling strategies and (c) predict cognitive and emotional/behavioural functioning. Methods Mothers experiencing high and low levels of psychosocial adversity (risk) were recruited antenatally and longitudinally assessed with their children. Mothers completed measures of settling strategies and infant sleep postnatally, and at 12 and 18 months, infant age. At five years, child sleep characteristics were measured via an actigraphy and maternal report; IQ and child adjustment were also assessed. Results Sleep disturbances observed in high-risk infants persisted at five years. Maternal involvement in infant settling was greater in high risk mothers, and predicted less optimal sleep at five years. Poorer five year sleep was associated with concurrent child anxiety/depression and aggression, but there was limited evidence for an influence of early sleep problems. Associations between infant/child sleep characteristics and IQ were also limited. Conclusions Early maternal over-involvement in infant settling is associated with less optimal sleep in children, which in turn, is related to child adjustment. The findings highlight the importance of supporting parents in the early development of good settling practices, particularly in high-risk populations.