Cross-translational studies in human and Drosophila identify markers of sleep loss

Inadequate sleep has become endemic, which imposes a substantial burden for public health and safety. At present, there are no objective tests to determine if an individual has gone without sleep for an extended period of time. Here we describe a novel approach that takes advantage of the evolutionary conservation of sleep to identify markers of sleep loss. To begin, we demonstrate that IL-6 is increased in rats following chronic total sleep deprivation and in humans following 30 h of waking. Discovery experiments were then conducted on saliva taken from sleep-deprived human subjects to identify candidate markers. Given the relationship between sleep and immunity, we used Human Inflammation Low Density Arrays to screen saliva for novel markers of sleep deprivation. Integrin αM (ITGAM) and Anaxin A3 (AnxA3) were significantly elevated following 30 h of sleep loss. To confirm these results, we used QPCR to evaluate ITGAM and AnxA3 in independent samples collected after 24 h of waking; both transcripts were increased. The behavior of these markers was then evaluated further using the power of Drosophila genetics as a cost-effective means to determine whether the marker is associated with vulnerability to sleep loss or other confounding factors (e.g., stress). Transcript profiling in flies indicated that the Drosophila homologues of ITGAM were not predictive of sleep loss. Thus, we examined transcript levels of additional members of the integrin family in flies. Only transcript levels of scab, the Drosophila homologue of Integrin α5 (ITGA5), were associated with vulnerability to extended waking. Since ITGA5 was not included on the Low Density Array, we returned to human samples and found that ITGA5 transcript levels were increased following sleep deprivation. These cross-translational data indicate that fly and human discovery experiments are mutually reinforcing and can be used interchangeably to identify candidate biomarkers of sleep loss

Internet use, eHealth literacy and attitudes toward computer/internet among people with schizophrenia spectrum disorders: a cross-sectional study in two distant European regions

Background: Individuals with schizophrenia spectrum disorders use the Internet for general and health-related purposes. Their ability to find, understand, and apply the health information they acquire online in order to make appropriate health decisions-known as eHealth literacy-has never been investigated. The European agenda strives to limit health inequalities and enhance mental health literacy. Nevertheless, each European member state varies in levels of Internet use and online health information-seeking. This study aimed to examine computer/Internet use for general and health-related purposes, eHealth literacy, and attitudes toward computer/Internet among adults with schizophrenia spectrum disorders from two distant European regions.Methods: Data were collected from mental health services of psychiatric clinics in Finland (FI) and Greece (GR). A total of 229 patients (FI = 128, GR = 101) participated in the questionnaire survey. The data analysis included evaluation of frequencies and group comparisons with multiple linear and logistic regression models.Results: The majority of Finnish participants were current Internet users (FI = 111, 87%, vs. GR = 33, 33%, P<.0001), while the majority of Greek participants had never used computers/Internet, mostly due to their perception that they do not need it. In both countries, more than half of Internet users used the Internet for health-related purposes (FI = 61, 55%, vs. GR = 20, 61%). The eHealth literacy of Internet users (previous and current Internet users) was found significantly higher in the Finnish group (FI: Mean = 27.05, SD 5.36; GR: Mean = 23.15, SD = 7.23, P<. 0001) upon comparison with their Greek counterparts. For current Internet users, Internet use patterns were significantly different between country groups. When adjusting for gender, age, education and disease duration, country was a significant predictor of frequency of Internet use, eHealth literacy and Interest. The Finnish group of Internet users scored higher in eHealth literacy, while the Greek group of never Internet users had a higher Interest in computer/Internet.Conclusions: eHealth literacy is either moderate (Finnish group) or low (Greek group). Thus, exposure to ICT and eHealth skills training are needed for this population. Recommendations to improve the eHealth literacy and access to health information among these individuals are provided

Diabetes Is an Independent Risk Factor for Severe Nocturnal Hypoxemia in Obese Patients. A Case-Control Study

Type 2 diabetes mellitus (T2DM) and obesity have become two of the main threats to public health in the Western world. In addition, obesity is the most important determinant of the sleep apnea-hypopnea syndrome (SAHS), a condition that adversely affects glucose metabolism. However, it is unknown whether patients with diabetes have more severe SAHS than non-diabetic subjects. The aim of this cross-sectional case-control study was to evaluate whether obese patients with T2DM are more prone to severe SAHS than obese non-diabetic subjects.Thirty obese T2DM and 60 non-diabetic women closely matched by age, body mass index, waist circumference, and smoking status were recruited from the outpatient Obesity Unit of a university hospital. The exclusion criteria included chronic respiratory disease, smoking habit, neuromuscular and cerebrovascular disease, alcohol abuse, use of sedatives, and pregnancy. Examinations included a non-attended respiratory polygraphy, pulmonary function testing, and an awake arterial gasometry. Oxygen saturation measures included the percentage of time spent at saturations below 90% (CT90). A high prevalence of SAHS was found in both groups (T2DM:80%, nondiabetic:78.3%). No differences in the number of sleep apnea-hypopnea events between diabetic and non-diabetic patients were observed. However, in diabetic patients, a significantly increase in the CT90 was detected (20.2+/-30.2% vs. 6.8+/-13,5%; p = 0.027). In addition, residual volume (RV) was significantly higher in T2DM (percentage of predicted: 79.7+/-18.1 vs. 100.1+/-22.8; p<0.001). Multiple linear regression analyses showed that T2DM but not RV was independently associated with CT90.T2DM adversely affects breathing during sleep, becoming an independent risk factor for severe nocturnal hypoxemia in obese patients. Given that SAHS is a risk factor of cardiovascular disease, the screening for SAHS in T2DM patients seems mandatory

Metabolic syndrome: definitions and controversies

Metabolic syndrome (MetS) is a complex disorder defined by a cluster of interconnected factors that increase the risk of cardiovascular atherosclerotic diseases and diabetes mellitus type 2. Currently, several different definitions of MetS exist, causing substantial confusion as to whether they identify the same individuals or represent a surrogate of risk factors. Recently, a number of other factors besides those traditionally used to define MetS that are also linked to the syndrome have been identified. In this review, we critically consider existing definitions and evolving information, and conclude that there is still a need to develop uniform criteria to define MetS, so as to enable comparisons between different studies and to better identify patients at risk. As the application of the MetS model has not been fully validated in children and adolescents as yet, and because of its alarmingly increasing prevalence in this population, we suggest that diagnosis, prevention and treatment in this age group should better focus on established risk factors rather than the diagnosis of MetS

Loss of Gnas Imprinting Differentially Affects REM/NREM Sleep and Cognition in Mice

It has been suggested that imprinted genes are important in the regulation of sleep. However, the fundamental question of whether genomic imprinting has a role in sleep has remained elusive up to now. In this work we show that REM and NREM sleep states are differentially modulated by the maternally expressed imprinted gene Gnas. In particular, in mice with loss of imprinting of Gnas, NREM and complex cognitive processes are enhanced while REM and REM–linked behaviors are inhibited. This is the first demonstration that a specific overexpression of an imprinted gene affects sleep states and related complex behavioral traits. Furthermore, in parallel to the Gnas overexpression, we have observed an overexpression of Ucp1 in interscapular brown adipose tissue (BAT) and a significant increase in thermoregulation that may account for the REM/NREM sleep phenotypes. We conclude that there must be significant evolutionary advantages in the monoallelic expression of Gnas for REM sleep and for the consolidation of REM–dependent memories. Conversely, biallelic expression of Gnas reinforces slow wave activity in NREM sleep, and this results in a reduction of uncertainty in temporal decision-making processes

Association between Insomnia Symptoms and Hemoglobin A1c Level in Japanese Men

Background: The evidence for an association between insomnia symptoms and blood hemoglobin A1c (HbA1c) level has been limited and inconclusive. The aim of this study was to assess whether each symptom of initial, middle, and terminal insomnia influences HbA 1c level in Japanese men. Methods: This cross-sectional study examined 1,022 male workers aged 22–69 years with no history of diabetes at a Japanese company’s annual health check-up in April 2010. High HbA1c was defined as a blood level of HbA1c $6.0%. Three types of insomnia symptoms (i.e., difficulty in initiating sleep, difficulty in maintaining sleep, and early morning awakening) from the previous month were assessed by 3 responses (i.e., lasting more than 2 weeks, sometimes, and seldom or never [reference group]). Results: The overall prevalence of high HbA1c was 5.2%. High HbA1c was positively and linearly associated with both difficulty in maintaining sleep (P for trend =.002) and early morning awakening (P for trend =.007). More specifically, after adjusting for potential confounding factors, high HbA1c was significantly associated with difficulty in maintaining sleep lasting more than 2 weeks (adjusted odds ratio, 6.79 [95 % confidence interval, 1.86–24.85]) or sometimes (2.33 [1.19–4.55]). High HbA1c was also significantly associated with early morning awakening lasting more than 2 weeks (3.96 [1.24–12.59]). Conclusion: Insomnia symptoms, particularly difficulty in maintaining sleep and early morning awakening, were found t

Autoadjusting-CPAP effect on serum Leptin concentrations in Obstructive Sleep Apnoea patients

© 2008 Drummond et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Changes in Inflammatory Biomarkers Across Weight Classes in a Representative US Population: A Link Between Obesity and Inflammation

Obesity has been linked with a chronic state of inflammation which may be involved in the development of metabolic syndrome, cardiovascular disease, non-alcoholic steatohepatitis, and even cancer. The objective of this study was to examine the association between obesity class and levels of inflammatory biomarkers from men and women who participated in the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Serum concentrations of C-reactive protein (CRP) and fibrinogen were measured among US participants of the 1999–2004 NHANES. We examined biomarker levels across different weight classes with normal weight, overweight, and obesity classes 1, 2, and 3 were defined as BMI of &lt;25.0, 25.0–29.9, 30.0–34.9, 35.0–39.9, and ≥40.0, respectively. With CRP levels for normal weight individuals as a reference, CRP levels nearly doubled with each increase in weight class: +0.11 mg/dl (95% CI, 0.06–0.16) for overweight, +0.21 mg/dl (95% CI, 0.16–0.27) for obesity class 1, +0.43 mg/dl (95% CI, 0.26–0.61) for obesity class 2, and +0.73 mg/dl (95% CI, 0.55–0.90) for obesity class 3. With normal weight individuals as a reference, fibrinogen levels increase with increasing weight class and were highest for obesity class 3 individuals, +93.5 mg/dl (95% CI, 72.9–114.1). Individuals with hypertension or diabetes have higher levels of CRP and fibrinogen levels compared to individuals without hypertension or diabetes, even when stratified according to BMI. There is a direct association between increasing obesity class and the presence of obesity-related comorbidities such as diabetes and hypertension with high levels of inflammatory biomarkers

Reliability of home CPAP titration with different automatic CPAP devices

<p>Abstract</p> <p>Background</p> <p>CPAP titration may be completed by automatic apparatus. However, differences in pressure behaviour could interfere with the reliability of pressure recommendations. Our objective was to compare pressure behaviour and effective pressure recommendations between three Automatic CPAP machines (Autoset Spirit, Remstar Auto, GK 420).</p> <p>Methods</p> <p>Sixteen untreated obstructive sleep apnea patients were randomly allocated to one of the 3 tested machines for a one-week home titration trial in a crossover design with a 10 days washout period between trials.</p> <p>Results</p> <p>The median pressure value was significantly lower with machine GK 420 (5.9 +/- 1.8 cm H₂O) than with the other devices both after one night and one week of CPAP titration (7.4 +/- 1.3 and 6.6 +/- 1.9 cm H₂O). The maximal pressure obtained over the one-week titration was significantly higher with Remstar Auto (12.6 +/- 2.4 cm H₂O, Mean +/- SD) than with the two other ones (10.9 +/- 1.0 and 11.0 +/- 2.4 cm H₂O). The variance in pressure recommendation significantly differed between the three machines after one night and between Autoset Spirit and the two other machines after 1 week.</p> <p>Conclusion</p> <p>Pressure behaviour and pressure recommendation significantly differ between Auto CPAP machines both after one night and one week of home titration.</p