Oxidative stress induced lung cancer and COPD : opportunities for epigenetic therapy

Reactive oxygen species (ROS) form as a natural by-product of the normal metabolism of oxygen and play important roles within the cell. Under normal circumstances the cell is able to maintain an adequate homeostasis between the formation of ROS and its removal through particular enzymatic pathways or via antioxidants. If however, this balance is disturbed a situation called oxidative stress occurs. Critically, oxidative stress plays important roles in the pathogenesis of many diseases, including cancer. Epigenetics is a process where gene expression is regulated by heritable mechanisms that do not cause any direct changes to the DNA sequence itself, and disruption of epigenetic mechanisms has important implications in disease. Evidence is emerging that histone deacetylases (HDACs) play decisive roles in regulating important cellular oxidative stress pathways including those involved with sensing oxidative stress and those involved with regulating the cellular response to oxidative stress. In particular aberrant regulation of these pathways by HDACs may play critical roles in cancer progression. In this review we discuss the current evidence linking epigenetics and oxidative stress and cancer, using chronic obstructive pulmonary disease and non-small cell lung cancer to illustrate the importance of epigenetics on these pathways within these disease settings. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Countermeasures to driver sleepiness : is the message getting through?

The most effective countermeasures to driver sleepiness (caffeine and a nap, ideally in combination) are not the most popular choice for UK drivers. Groups susceptible to driver sleepiness (OSA patients and truck drivers) do not favour effective countermeasures to driver sleepiness. Prior experience of driver sleepiness does not promote an effective choice of countermeasure.

Physical activity patterns and correlates among adults from a developing country : the Sri Lanka Diabetes and Cardiovascular Study

OBJECTIVE: To evaluate patterns of physical activity (PA), the prevalence of physical inactivity and the relationships between PA and sociodemographic, clinical and biochemical parameters among Sri Lankan adults. DESIGN: Descriptive cross-sectional study. SETTING: Nationally representative population-based survey conducted in Sri Lanka. SUBJECTS: Data on PA and associated details were obtained from 5000 adults. PA was assessed using the International Physical Activity Questionnaire (short-form). A binary logistic regression analysis was performed using the dichotomous variable ‘health-enhancing PA’ (05‘active’, 15‘inactive’). RESULTS: Sample size was 4485. Mean age was 46.1 (SD 15.1) years, 39.5% were males. The mean weekly total MET (metabolic equivalents of task) minutes of PA among the study population was 4703 (SD 4369). Males (5464 (SD 5452)) had a significantly higher weekly total MET minutes than females (4205 (SD 3394); P,0.001). Rural adults (5175 (SD 4583)) were significantly more active than urban adults (2956 (SD 2847); P<0.001). Tamils had the highest mean weekly total MET minutes among ethnicities. Those with tertiary education had lowest mean weekly total MET minutes. In all adults 60.0% were in the ‘highly active’ category, while only 11.0% were ‘inactive’ (males 14.6%, females 8.7%; P<0.001). Of the ‘highly active’ adults, 85.8% were residing in rural areas. Results of the binary logistic regression analysis indicated that female gender (OR52?1), age .70 years (OR53.8), urban living (OR52.5), Muslim ethnicity (OR52.7), tertiary education (OR53.6), obesity (OR51.8), diabetes (OR51.6), hypertension (OR51.2) and metabolic syndrome (OR51.3) were all associated with significantly increased odds of being physically ‘inactive’. CONCLUSIONS: The majority of Sri Lankan adults were ‘highly active’ physically. Female gender, older age, urban living, Muslim ethnicity and tertiary education were all significant predictors of physical inactivity. Physical inactivity was associated with obesity, diabetes, hypertension and metabolic syndrome.

Self-regulation from birth to age seven : associations with maternal mental health, parenting, and social, emotional and behavioural outcomes for children

Self-regulation refers to our individual capacities to regulate our behaviours, emotions, and thoughts, with these skills developing rapidly across early childhood. This thesis examined sleep, emotional, and cognitive regulation development, and related parental influences, for children participating in the Longitudinal Study of Australian Children. Important longitudinal associations among children's self-regulation, maternal mental health, parenting, and later behaviour problems for children were also investigated. A unique contribution of this research was a prevalence estimate of early childhood self-regulation problems in Australian children that was documented for the first time.

On-road driver sleepiness : what are Australian drivers experiences and awareness of sleepiness while driving?

Objectives: Driver sleepiness contributes substantially to road crash incidents. Simulator and on-road studies clearly reveal an impairing effect from sleepiness for driving ability. However, drivers might not appreciate the dangerousness of driving while sleepy and this could translate to their on-road driving behaviours. This study sought to determine drivers’ on-road experiences of sleepiness, their sleep habits, and personal awareness of the signs of sleepiness. Methods: Participants were a random selection of 92 drivers travelling on a major highway in the state of Queensland, Australia, who were stopped by Police as part of routine drink driving operations. Participants completed a brief questionnaire that included: demographic details, awareness and on-road experiences of sleepy driving, and sleep habits. A modified version of the Karolinska Sleepiness Scale (KSS) was used to assess subjective sleepiness during the last 15 minutes of driving. Results: Participants rating of subjective sleepiness was quite low with 90% reporting at or below 3 on the KSS. Participants were reasonably aware of the signs of sleepiness; with a number of these correlated with on-road experiences. The participants sleep debt correlated with their alertness (r = -.30) and the hours spent driving (r = .38). Conclusions: These results suggest that drivers had moderate or substantial experience of driving when sleepy and many were aware of the signs of sleepiness. As many of the participants reported driving long distances after suboptimal sleep durations, it is possible that their risk perception of the dangerousness of sleepy driving maybe erroneous.

Postpartum sleepiness and sleepy driving in Australian mothers

This paper reports on a prospective study investigating the prevalence of maternal postpartum fatigue and sleepiness and highlights the potential increased crash risk faced by mothers when driving in the postpartum period. Twenty-four mothers from across Australia completed a sleep and driving diary for seven consecutive days at three time points; when their baby was 6, 12 and 18 weeks old. The results showed that the mothers’ sleep varied within the sample, however on average sleep disruption and lack of sleep consolidation was experienced. A high proportion of the mothers reported fatigue and sleepiness impacting their functioning early in the postpartum period, with sleepiness being more enduring throughout the period. Of concern, a high proportion of driving journeys undertaken by the mothers were during high levels of sleepiness, particularly early in the postpartum period and during late night and early hours of the day. These findings have highlighted the need to educate mothers about the potential increased safety risk of driving during the postpartum period and identified key information that should be conveyed.

The effect of sleep deprivation on BOLD activity elicited by a divided attention task

Sleep loss, widespread in today’s society and associated with a number of clinical conditions, has a detrimental effect on a variety of cognitive domains including attention. This study examined the sequelae of sleep deprivation upon BOLD fMRI activation during divided attention. Twelve healthy males completed two randomized sessions; one after 27 h of sleep deprivation and one after a normal night of sleep. During each session, BOLD fMRI was measured while subjects completed a cross-modal divided attention task (visual and auditory). After normal sleep, increased BOLD activation was observed bilaterally in the superior frontal gyrus and the inferior parietal lobe during divided attention performance. Subjects reported feeling significantly more sleepy in the sleep deprivation session, and there was a trend towards poorer divided attention task performance. Sleep deprivation led to a down regulation of activation in the left superior frontal gyrus, possibly reflecting an attenuation of top-down control mechanisms on the attentional system. These findings have implications for understanding the neural correlates of divided attention and the neurofunctional changes that occur in individuals who are sleep deprived.

Paternal postnatal depressive symptoms, infant sleeping and feeding behaviors, and rigid parental regulation : a correlational study

Paternal postnatal depression (PND) is now recognized as a serious and prevalent problem, associated with poorer well-being and functioning of all family members. Aspects of infant temperament, sleeping and feeding perceived by parents as problematic are associated with maternal PND, however, less is known about paternal PND. This study investigated depressive symptoms (Edinburgh postnatal depression scale (EPDS)) in 219 fathers of infants aged from 1 to 24 weeks (median 7.0 weeks). Infant predictor variables were sleeping problems, feeding problems and both mother and father reported temperament. Control variables were partner’s support, other support and life events. Rigidity of parenting beliefs regarding infant regulation was also measured as a potential moderating factor. Infant feeding difficulties were associated with paternal depressive symptoms, subsuming the variance associated with both sleep problems and temperament. This relationship was not moderated by regulation beliefs. It was concluded that infant feeding is important to fathers. Fathers of infants with feeding difficulties may not be able to fulfill their idealized construction of involved fatherhood. Role incongruence may have an etiological role in paternal PND.

The impact of relaxing music on insomnia-related thoughts and behaviours

Insomnia is a pervasive problem involving poor sleep quality and quantity. Previous research has suggested that music listening can help alleviate insomnia, but exactly how music helps sleep problems has not been determined. A greater understanding of these processes could help practitioners to design more effective music-based insomnia treatments. This randomised controlled trial was designed to assess the influences of nightly music listening on the sleep-related thoughts and behaviours described in Harvey’s (2002) cognitive model of insomnia maintenance. University students, including a range of good and poor sleepers, were randomly assigned to a music listening group or a control group and were assessed before and after a two-week music listening intervention. Measures included a range of self-report scales, each assessing an element of Harvey’s cognitive model. During the intervention, the music listening group was asked to listen to provided music for at least 20 minutes each night. The control group was asked to maintain their regular nightly routines. Results indicated that the music listening group significantly improved on most of the factors theorised to influence sleep quality, although their actual sleep quality did not significantly improve. The control group did not change significantly on any measures. The results of this study suggest that music listening can have positive impacts on a range of factors theorised to influence sleep quality. However, as the music was not shown to actually improve sleep quality, Harvey’s cognitive model explanation of music’s effect on sleep quality may require further investigation.

Napping, development and health from 0 to 5 years : a systematic review

Background Duration and quality of sleep affect child development and health. Encouragement of napping in preschool children has been suggested as a health-promoting strategy. Objectives The aim of this study is to assess evidence regarding the effects of napping on measures of child development and health. Design This study is a systematic review of published, original research articles of any design. Subjects Children aged 0–5 years. Method Electronic database search was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessment of research quality was carried out following a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) protocol. Results Twenty-six articles met inclusion criteria. These were of heterogeneous quality; all had observational designs (GRADE-low). Development and health outcomes included salivary cortisol, night sleep, cognition, behaviour, obesity and accidents. The findings regarding cognition, behaviour and health impacts were inconsistent, probably because of variation in age and habitual napping status of the samples. The most consistent finding was an association between napping and later onset, shorter duration and poorer quality of night sleep, with evidence strongest beyond the age of 2 years. Limitations Studies were not randomised. Most did not obtain data on the children's habitual napping status or the context of napping. Many were reliant on parent report rather than direct observation or physiological measurement of sleep behaviour. Conclusions The evidence indicates that beyond the age of 2 years napping is associated with later night sleep onset and both reduced sleep quality and duration. The evidence regarding behaviour, health and cognition is less certain. There is a need for more systematic studies that use stronger designs. In preschool children presenting with sleep problems clinicians should investigate napping patterns.

The on-road experiences and awareness of sleepiness in a sample of Australian highway drivers: A roadside driver sleepiness study

Objective Driver sleepiness contributes substantially to road crash incidents. Simulator and on-road studies clearly reveal an impairing effect from sleepiness on driving ability. However, the degree to which drivers appreciate the dangerousness of driving while sleepy is somewhat unclear. This study sought to determine drivers’ on-road experiences of sleepiness, their prior sleep habits, and personal awareness of the signs of sleepiness. Methods Participants were a random selection of 92 drivers travelling on a major highway in the state of Queensland, Australia, who were stopped by police as part of routine drink driving operations. Participants completed a brief questionnaire that included demographic information, sleepy driving experiences (signs of sleepiness and on-road experiences of sleepiness), and prior sleep habits. A modified version of the Karolinska Sleepiness Scale (KSS) was used to assess subjective sleepiness in the 15 minutes prior to being stopped by police. Results Participants rating of subjective sleepiness were quite low, with 90% reporting being alert to extremely alert on the KSS. Participants were reasonably aware of the signs of sleepiness, with many signs of sleepiness associated with on-road experiences of sleepiness. Additionally, the number of hours spent driving was positively correlated with the drivers’ level of sleep debt. Conclusions The results suggest the participants had moderate experience of driving while sleepy and many were aware of the signs of sleepiness. The relationship between driving long distances and increased sleep debt is a concern for road safety – increased education regarding the dangers of sleepy driving seems warranted.

A study protocol: A community pharmacy-based intervention for improving the management of sleep disorders in the community settings

Background Sleep disorders are very common in the community and are estimated to affect up to 45% of the world’s population. Pharmacists are in a position to give advice and provide appropriate services to individuals who are unable to easily access medical care. The purpose of this study is to develop an intervention to improve the management of sleep disorders in the community. The aims are: (1) to evaluate the effectiveness of a community pharmacy-based intervention in managing sleep disorders; (2) to evaluate the role of actigraph as an objective measure in monitoring certain sleep disorders, and; (3) to evaluate the extended role of community pharmacists in managing sleep disorders. This intervention is developed to monitor individuals undergoing treatment and overcome the difficulties in validating self-reported feedback. Method/design This is a community-based intervention, prospective, controlled trial, with one intervention group and one control group, comparing individuals receiving a structured intervention with those receiving usual care for sleep-related disorders at community pharmacies. Discussion This study will demonstrate the utilisation and efficacy of community pharmacy-based intervention to manage sleep disorders in the community, and will assess the possibility of implementing this intervention into the community pharmacy workflow.

The influence of family history of hypertension on disease prevalence and associated metabolic risk factors among Sri Lankan adults

Background Hypertension is a major contributor to the global non-communicable disease burden. Family history is an important non-modifiable risk factor for hypertension. The present study aims to describe the influence of family history (FH) on hypertension prevalence and associated metabolic risk factors in a large cohort of South Asian adults, from a nationally representative sample from Sri Lanka. Methods A cross-sectional survey among 5,000 Sri Lankan adults, evaluating FH at the levels of parents, grandparents, siblings and children. A binary logistic regression analysis was performed in all patients with ‘presence of hypertension’ as dichotomous dependent variable and using family history in parents, grandparents, siblings and children as binary independent variables. The adjusted odds ratio controlling for confounders (age, gender, body mass index, diabetes, hyperlipidemia and physical activity) are presented below. Results In all adults the prevalence of hypertension was significantly higher in patients with a FH (29.3 %, n = 572/1951) than those without (24.4 %, n = 616/2530) (p < 0.001). Presence of a FH significantly increased the risk of hypertension (OR:1.29; 95 % CI:1.13-1.47), obesity (OR:1.36; 95 % CI: 1.27–1.45), central obesity (OR:1.30; 95 % CI 1.22–1.40) and metabolic syndrome (OR:1.19; 95 % CI: 1.08–1.30). In all adults presence of family history in parents (OR:1.28; 95 % CI: 1.12–1.48), grandparents (OR:1.34; 95 % CI: 1.20–1.50) and siblings (OR:1.27; 95 % CI: 1.21–1.33) all were associated with significantly increased risk of developing hypertension. Conclusions Our results show that the prevalence of hypertension was significantly higher in those with a FH of hypertension. FH of hypertension was also associated with the prevalence of obesity, central obesity and metabolic syndrome. Individuals with a FH of hypertension form an easily identifiable group who may benefit from targeted interventions.

Colonoscopy preparation in children: Safety, efficacy, and tolerance of high- versus low-volume cleansing methods

Background: The use of large-volume electrolyte balanced solutions as preparation for colonoscopy often results in poor patient compliance and acceptance. The tolerance, safety, and efficacy of high-versus low volume colon-cleansing methods as preparation for colonoscopy in children were compared by randomized operator-blinded trial. Methods: Twenty-nine children ages 3.6-14.6 years had either high-volume nasogastric balanced polyethylene glycol electrolyte lavage (20 ml/kg/h) until the effluent was clear (n = 15), or two oral doses of sodium phosphate solution (22.5-45 ml) separated by oral fluid intake (n = 14). Results: Both preparations were equally effective. The low-volume preparation was better tolerated and caused less discomfort that the high-volume preparation, judging by serial nurse observations. The incidence of abdominal symptoms, diarrhea, sleep disturbance, and vomiting was not significantly different between the two groups. Both groups had a small reduction in mean hematocrit and serum calcium levels. The sodium phosphate preparation caused increases in mean serum sodium concentrations from 140 to 145 mmol/L and serum phosphate concentrations from 1.41 to 2.53 mmol/L. Ten hours after the commencement of the preanesthetic fast, these concentrations had returned to normal. Conclusions: There are advantages in terms of tolerance, discomfort, and case of administration with acceptable colonic cleansing with the use of the less-invasive oral sodium phosphate low-volume colon-cleansing preparation in children. Safe use requires ensuring an adequate oral fluid intake during the preparation time and avoidance of use in patients with renal insufficiency.

“I have to rest all the time because you are not allowed to play”: Exploring children’s perceptions of autonomy during sleep-time in long day care services

Daytime sleep is a significant part of the daily routine for children attending early childhood education and care (ECEC) services in Australia and many other countries. The practice of sleep-time can account for a substantial portion of the day in ECEC and often involves a mandated sleep/rest period for all children, including older preschool-aged children. Yet, there is evidence that children have a reduced need for daytime sleep as they approach school entry age and that continuation of mandated sleep-time in ECEC for preschool-aged children may have a negative impact on their health, development, learning and well-being. Mandated sleep-time practices also go against current quality expectations for services to support children’s agency and autonomy in ECEC. This study documents children’s reports of their experiences of sleep-time in ECEC. Semi-structured interviews were conducted with 54 preschool-aged children (44–63 months) across four long day ECEC services that employed a range of sleep-time practices. Findings provide a snapshot of children’s views and experiences of sleep-time and perceptions of autonomy-supportive practices. These provide a unique platform to support critical reflection on sleep-time policies and practices, with a view to continuous quality improvement in ECEC. This study forms part of a programme of work from the Sleep in Early Childhood research group. Our work examines sleep practices in ECEC, the subsequent staff, parent and child experiences and impacts on family and child learning and development outcomes.