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1.  Adiposity, serum lipid levels, and allergic sensitization in Chinese men and women 
Background
Obesity and allergic diseases have increased dramatically in recent decades. While adiposity has been associated with asthma, associations with allergic sensitization have been inconsistent.
Objective
To examine the association of adiposity and lipid profiles with allergic sensitization.
Methods
This study included 1,187 rural Chinese twins (653 men) aged 18-39 years, with skin prick tests (SPT), anthropometric and DEXA-assessed adiposity measures, and lipid assessments. Allergic sensitization was defined as positive SPT to ≥1 allergen (9 foods and 5 aeroallergens tested). We applied gender-stratified generalized estimating equations to assess the association of adiposity and serum lipids with allergic sensitization, and structural equation models to estimate the genetic/environmental influences on any observed associations.
Results
Males had lower percent body fat (%BF) (13.9% vs. 28.8%) but higher rates of allergic sensitization (56.2% vs. 36.7%) than females. Males in the highest %BF quartile were 2.1 times more likely sensitized than the lowest quartile (95%CI 1.3-3.5, P-trend=0.003). In males, the risk of allergic sensitization increased with HDL<40 mg/dl (OR=4.0, 95%CI 1.8-9.2) and higher LDL quartiles (P-trend=0.007). This appeared to be partially explained by shared genetic factors between serum lipid levels and allergic sensitization. In females, lower HDL was associated with increased risk of allergic sensitization.
Conclusions
In this relatively lean Chinese population, higher %BF, lower HDL and higher LDL were associated with greater risk of allergic sensitization, most notable in males. The observed associations between adiposity, serum lipids and allergic sensitization in males appear to be partially explained by common genetic influences on these traits.
doi:10.1016/j.jaci.2008.11.032
PMCID: PMC2697621  PMID: 19135238
DEXA; Body mass index; Adiposity; Serum lipids; Sensitization
2.  SLEEP DURATION AND AMBULATORY BLOOD PRESSURE IN BLACK AND WHITE ADOLESCENTS 
Hypertension  2012;59(3):747-752.
Self-reported short sleep duration is linked to higher blood pressure and incident hypertension in adults. Few studies have examined sleep and blood pressure in younger samples. We evaluated the associations between actigraphy-assessed time spent asleep and ambulatory blood pressure in adolescents. Participants were 246 black and white adolescents (mean age = 15.7) who were free from cardiovascular or kidney disease and were not taking sleep, cardiovascular, or psychiatric medications. Sleep duration and efficiency were assessed with in-home wrist actigraphy and sleep diaries across one week; ambulatory blood pressure monitoring was used to obtain 24-hour, sleep, wake blood pressure, and sleep-wake blood pressure ratios across two full days and nights. Results showed that shorter actigraphy-assessed sleep across one week was related to higher 48-hour blood pressure and higher nighttime blood pressure. Shorter sleep was also related to a higher systolic blood pressure sleep-wake ratio. These results were independent of age, race, sex, and body mass index. Follow-up analyses by race revealed that associations between sleep duration and blood pressure were largely present in white, but not black, adolescents. These data are consistent with the hypothesis that the cardiovascular consequences of short sleep may begin as early as adolescence.
doi:10.1161/HYPERTENSIONAHA.111.184770
PMCID: PMC3314491  PMID: 22275538
ambulatory blood pressure; sleep duration; actigraphy; adolescent; race
3.  The Association of Short and Long Sleep Durations with Insulin Sensitivity In Adolescents 
The Journal of pediatrics  2010;158(4):617-623.
Objective
To characterize the relationship between insulin sensitivity, assessed by the homeostasis model of insulin (HOMA), and objective measurements of sleep duration in adolescents.
Study design
Cross-sectional analysis from two examinations conducted in the Cleveland Children’s Sleep and Health Cohort (n=387; 43% minorities). Biochemical and anthropometry measurements made in a Clinical Research Unit. Sleep duration measured by actigraphy.
Results
Decreased sleep duration was associated with increased adiposity and minority race. Sleep duration had a quadratic “u-shape” association with HOMA. When adjusted for age, sex, race, preterm status and activity, adolescents who slept 7.75 hours had the lowest predicted HOMA (1.96 [95% CI: 1.82, 2.10]), and adolescents who slept 5.0 hours or 10.5 hours had HOMA indices that were about 20% higher (2.36 [95% CI: 1.94, 2.86] and 2.41 [95% CI: 1.93, 3.01], respectively). After adjusting for adiposity, the association between shorter sleep and HOMA was appreciably attenuated, but the association with longer sleep persisted.
Conclusions
Shorter and longer sleep durations are associated with decreased insulin sensitivity in adolescents. Whereas the association between shorter sleep duration with insulin sensitivity is likely explained by the association between short sleep and obesity, association between longer sleep and insulin sensitivity is independent of obesity.
doi:10.1016/j.jpeds.2010.09.080
PMCID: PMC3076647  PMID: 21146189
Sleep; insulin resistance; obesity
4.  HIGH PREVALENCE OF AEROALLERGEN SENSITIZATION AMONG INFANTS OF ATOPIC PARENTS 
The Journal of pediatrics  2006;149(4):505-511.
Objective
To present methodology to identify atopic parents and determine the prevalence of sensitization to 15 aeroallergens in their infant offspring.
Study design
A birth cohort of infants was identified from birth records; an infant was enrolled if 1 of the parents reported allergy respiratory symptoms and had a positive skin prick test (SPT) to a common aeroallergen. At age 1 year, these infants were tested to the same aeroallergens.
Results
Of the 680 enrolled infants, 28.4% were SPT+ to 1 or more aeroallergens and/or food, and 18.0% were positive to 1 or more aeroallergens. By category of allergens, 9.7% were sensitized to pollens, 7.5% to molds, 4.3% to house dust mite and/or cockroach, and 3.4% to dog and/or cat. Of the infants who were positive to an aeroallergen, 65.7% remained positive at age 2 years.
Conclusions
Infants born to atopic parents with percutaneous sensitization to aeroallergens are at increased risk for aeroallergen sensitization during infancy, which persists to age 2 years. These findings suggest that current clinical practices, which generally avoid skin testing before age 2 years, be reassessed in this population of high-risk children.
doi:10.1016/j.jpeds.2006.06.035
PMCID: PMC2233934  PMID: 17011322
5.  Gender-Specific Association of Sleep Duration with Blood Pressure in Rural Chinese Adults 
Sleep medicine  2011;12(7):693-699.
Background
There are limited data about the role of gender on the relationship between sleep duration and blood pressure (BP) from rural populations.
Methods
We conducted a cross-sectional rural population-based study. This report includes 1,033 men and 783 women aged 18–65 years from a cohort of twins enrolled in Anhui, China, between 2005 and 2008. Sleep duration was derived from typical bedtime, wake-up time, and sleep latency as reported on a standard sleep questionnaire. Primary outcomes included measured systolic blood pressure (SBP) and diastolic blood pressure (DBP). High blood pressure (HBP) was defined as SBP≥130 mmHg, DBP ≥85 mmHg, or physician diagnosed hypertension. Linear and logistic regression models were used to assess gender-specific associations between sleep duration and BP or HBP, respectively, with adjustment for known risk factors including adiposity and sleep-related disorder risk from the questionnaires. Generalized estimating equations were used to account for intra-twin pair correlations.
Results
Compared with those sleeping 7 to less than 9 hours, women sleeping <7 hours had a higher risk of HBP (odds ratios [ORs] 3.0, 95% confidence interval [CI], 1.4–6.6); men sleeping ≥9 hours had a higher risk of HBP (ORs=1.5, 95%CI: 1.1–2.2).
Conclusions
Among rural Chinese adults, a gender-specific association of sleep duration with BP exists such that HBP is associated with short sleep duration in women and long sleep duration in men. Longitudinal studies are needed to further examine the temporal relationship and biological mechanisms underlying sleep duration and BP in this population. Our findings underscore the potential importance of appropriate sleep duration for optimal blood pressure.
doi:10.1016/j.sleep.2010.12.019
PMCID: PMC3755492  PMID: 21764369
sleep duration; high blood pressure; gender difference; rural Chinese
6.  Temporal daily associations between pain and sleep in adolescents with chronic pain versus healthy adolescents 
Pain  2010;151(1):220-225.
Adolescents with chronic pain frequently report sleep disturbances, particularly short sleep duration, night wakings, and poor sleep quality. Prior research has been limited by assessment of subjectively reported sleep only and lack of data on daily relationships between sleep and pain. The current study utilized multilevel modeling to compare daily associations between sleep and pain in adolescents with chronic pain and healthy adolescents. Ninety-seven adolescents (n=39 chronic pain; n=58 healthy) aged 12–18, 70.1% female participated. Adolescents completed pain diary ratings (0–10 NRS) and actigraphic sleep monitoring for 10 days. Actigraphic sleep variables (duration, efficiency, WASO) and self-reported sleep quality were tested as predictors of next-day pain, and daytime pain was tested as a predictor of sleep that night. Effects of age, gender, study group, and depressive symptoms on daily associations between sleep and pain were also tested. Multivariate analyses revealed that nighttime sleep (p<.001) and minutes awake after sleep onset (WASO) (p<.05) predicted next-day pain, with longer sleep duration and higher WASO associated with higher pain. Contrary to hypotheses, neither nighttime sleep quality nor sleep efficiency predicted pain the following day. The interaction between nighttime sleep efficiency and study group was significant, with adolescents with pain showing stronger associations between sleep efficiency and next day pain than healthy participants (p=.05). Contrary to hypotheses, daytime pain did not predict nighttime sleep. Daily associations between pain and sleep suggest that further work is needed to identify specific adolescent sleep behaviors (e.g., compensatory sleep behaviors) that may be targeted in interventions.
doi:10.1016/j.pain.2010.07.016
PMCID: PMC2939216  PMID: 20719433
pain; chronic pain; actigraphy; adolescents; sleep; multilevel-modeling
7.  Genetic and Environmental Contributions to Allergen Sensitization in a Chinese Twin Study 
Background:
Allergic disease is on the rise worldwide. Effective prevention of allergic disease requires comprehensive understanding of the factors that contribute to its intermediate phenotypes, such as sensitization to common allergens.
Objective:
To estimate the degree of genetic and environmental contributions to sensitization to food or aeroallergens.
Methods:
Sensitization was defined as a positive skin prick test to an allergen. We calculated the zygosity-specific concordance rates and odds ratios (ORs) for sensitization to food and aeroallergens in 826 Chinese twin pairs (472 MZ and 354 DZ) aged 12 to 28 years. We also applied structural equation modeling procedures to estimate genetic and environmental influences on sensitization.
Results:
The concordance rates and risk of sensitization in one twin given the presence vs. the absence of sensitization in the other twin were higher in MZ twins than those in DZ twins. However, a large number of MZ twins were discordant in sensitization to common allergens. These observations suggest both genetic and environmental factors influence sensitization. Consistently, the estimated heritability and individual environmental components of the liability to sensitization ranged from 0.51 to 0.68 and 0.32 to 0.49, respectively, based on the best-fitted structural equation model. We also observed high phenotypic correlations between sensitization to two aeroallergens (cockroach and dust mite: 0.83) and two food allergens (peanut and shellfish: 0.58), but only moderate correlations for the pairs between sensitization to a food and an aeroallergen (0.31-0.46). The shared genetic and environmental factors between paired sensitizations contribute to the observed correlations.
Conclusion:
We demonstrated that sensitization to common food and aeroallergens were influenced by both genetic and environmental factors. Moreover, we found that paired allergen sensitizations might share some common sets of genes and environmental factors. This study underscores the need to further delineate unique and/or pleiotropic genetic and environmental factors for allergen sensitization.
doi:10.1111/j.1365-2222.2009.03228.x
PMCID: PMC2756049  PMID: 19302247
Twin; sensitization; positive SPT; structural equation modeling; heritability; environmental factors
8.  Sleep Duration, Sleep Regularity, Body Weight, and Metabolic Homeostasis in School-aged Children 
Pediatrics  2011;127(2):e345-e352.
OBJECTIVE:
The goal was to explore the effects of duration and regularity of sleep schedules on BMI and the impact on metabolic regulation in children.
METHODS:
Sleep patterns of 308 community-recruited children 4 to 10 years of age were assessed with wrist actigraphs for 1 week in a cross-sectional study, along with BMI assessment. Fasting morning plasma levels of glucose, insulin, lipids, and high-sensitivity C-reactive protein also were measured for a subsample.
RESULTS:
Children slept 8 hours per night, on average, regardless of their weight categorization. A nonlinear trend between sleep and weight emerged. For obese children, sleep duration was shorter and showed more variability on weekends, compared with school days. For overweight children, a mixed sleep pattern emerged. The presence of high variance in sleep duration or short sleep duration was more likely associated with altered insulin, low-density lipoprotein, and high-sensitivity C-reactive protein plasma levels. Children whose sleep patterns were at the lower end of sleep duration, particularly in the presence of irregular sleep schedules, exhibited the greatest health risk.
CONCLUSIONS:
Obese children were less likely to experience “catch-up” sleep on weekends, and the combination of shorter sleep duration and more-variable sleep patterns was associated with adverse metabolic outcomes. Educational campaigns, aimed at families, regarding longer and more-regular sleep may promote decreases in obesity rates and may improve metabolic dysfunction trends in school-aged children.
doi:10.1542/peds.2010-0497
PMCID: PMC3025425  PMID: 21262888
sleep duration; obesity; children; lipids; insulin resistance; inflammation
9.  Sleep, aging, and lifespan in Drosophila 
BMC Neuroscience  2010;11:56.
Background
Epidemiological studies in humans suggest that a decrease in daily sleep duration is associated with reduced lifespan, but this issue remains controversial. Other studies in humans also show that both sleep quantity and sleep quality decrease with age. Drosophila melanogaster is a useful model to study aging and sleep, and inheriting mutations affecting the potassium current Shaker results in flies that sleep less and have a shorter lifespan. However, whether the link between short sleep and reduced longevity exists also in wild-type flies is unknown. Similarly, it is unknown whether such a link depends on sleep amount per se, rather than on other factors such as waking activity. Also, sleep quality has been shown to decrease in old flies, but it remains unclear whether aging-related sleep fragmentation is a generalized phenomenon.
Results
We compared 3 short sleeping mutant lines (Hk1, HkY and Hk2) carrying a mutation in Hyperkinetic, which codes for the beta subunit of the Shaker channel, to wild-type siblings throughout their entire lifespan (all flies kept at 20°C). Hk1 and HkY mutants were short sleeping relative to wild-type controls from day 3 after eclosure, and Hk2 flies became short sleepers about two weeks later. All 3 Hk mutant lines had reduced lifespan relative to wild-type flies. Total sleep time showed a trend to increase in all lines with age, but the effect was most pronounced in Hk1 and HkY flies. In both mutant and wild-type lines sleep quality did not decay with age, but the strong preference for sleep at night declined starting in "middle age". Using Cox regression analysis we found that in Hk1 and HkY mutants and their control lines there was a negative relationship between total sleep amount during the first 2 and 4 weeks of age and hazard (individual risk of death), while no association was found in Hk2 flies and their wild-type controls. Hk1 and HkY mutants and their control lines also showed an association between total daily wake activity over the first 2 and 4 weeks of age and hazard. However, when both sleep duration and wake activity were used in the same regression, the effects of activity were much reduced, while most of the sleep effects remained significant. Finally, Hk1 flies and wild-type siblings were also tested at 25°C, and results were similar to those at 20°C. Namely, Hk1 mutants were short sleeping, hyperactive, and short lived relative to controls, and sleep quality in both groups did not decrease with age.
Conclusions
Different Hk mutations affect the sleep phenotype, and do so in an age-dependent manner. In 4 of the 6 lines tested sleep associates significantly with lifespan variation even after any effect of activity is removed, but activity does not associate significantly with lifespan after the effects of sleep are removed. Thus, in addition to environmental factors and genetic background, sleep may also affect longevity. Sleep quality does not necessarily decay as flies age, suggesting that aging-related sleep fragmentation may also depend on many factors, including genetic background and rearing conditions.
doi:10.1186/1471-2202-11-56
PMCID: PMC2871268  PMID: 20429945
10.  Sleep duration and its correlates in middle-aged and elderly Chinese women: the Shanghai Women’s Health Study 
Sleep medicine  2012;13(9):1138-1145.
Background
Abnormal sleep duration, either long or short, is associated with disease risk and mortality. Little information is available on sleep duration and its correlates among Chinese women.
Methods
Using information collected from 68,832 women who participated in the Shanghai Women’s Health Study (SWHS), we evaluated sleep duration and its correlations with sociodemographic and lifestyle factors, health status, and anthropometric measurements and their indexes using polynomial logistic regression.
Results
The mean age of the study population was 59.6 years (SD=9.0; range: 44.6–79.9 years) at time of sleep duration assessment. Approximately 80% of women reported sleeping 6–8 hours per day, 11.5% slept five hours or less, and 8.7% slept nine hours or more. As expected, age was the strongest predictor for sleep duration and was negatively correlated with sleep duration. In general, sleep duration was positively associated with energy intake, intakes of total meat and fruits, body mass index (BMI), waist-hip ratio (WHR), and waist circumference (WC) after adjustment for age and other factors. Both short and long sleep duration were negatively associated with education level, family income, and leisure-time physical activity and positively associated with number of live births, history of night shift work, and certain chronic diseases, compared to sleep duration around seven hours/day (6.5–7.4 hours/day). Short sleep duration was related to tea consumption and passive smoking. Long sleep duration was related to menopausal status and marital status.
Conclusions
In this large, population-based study, we found that sleep duration among middle-aged and elderly Chinese women was associated with several sociodemographic and lifestyle factors and with disease status. The main limitation of the study is the cross-sectional design that does not allow us to draw any causal inference. However, this study provides information for future investigation into the nature of these associations so that recommendations can be developed to reduce sleep problems in middle-aged and elderly Chinese women. It also provides important information on potential confounders for investigation of sleep duration on health outcomes in this population.
doi:10.1016/j.sleep.2012.06.014
PMCID: PMC3474879  PMID: 22938861
Sleep duration; socio-economic factor; lifestyle; health status; BMI; correlation; Chinese
11.  Short Sleep Duration Is Associated with Insulin Resistance Independent of Adiposity in Chinese Adult Twins 
Sleep medicine  2011;12(9):914-919.
Objective
To investigate the association between sleep duration and insulin resistance in rural Chinese adults and examine whether any such associations are independent of adiposity.
Methods
This is a cross-sectional analysis of 854 men and 640 women aged 20 to 70 years from the Anqing Twin Cohort. The following measures were obtained for each subject: Body mass index (BMI) and percentage of trunk fat (%TF), fasting plasma glucose, homeostatic model assessment of insulin resistance index (HOMA-IR), self-reported sleep duration, and measures of snoring and sleep disturbance from the Pittsburgh Sleep Quality Indices (PSQI) questionnaire modified for a Chinese population. Multivariate linear regressions were applied to examine the association of sleep duration with HOMA-IR, with and without adjustment for adiposity variables, along with other relevant covariates.
Results
In this sample of relatively lean rural Chinese adults, short sleep duration was associated with HOMA-IR in women but not in men. In women, short (≤7 hrs/night) sleep duration was associated with a higher HOMA-IR (p=0.003) compared with normal sleep duration (>7 to ≤8 hrs/night) after adjustment for all the covariates except adiposity. Further adjustment for BMI or %TF attenuated the sleep-HOMA-IR association, but the association remained significant upon adjustment for BMI (p=0.013); and upon adjustment for %TF (p=0.026). Long sleep duration (>8 hrs/night) was not significantly associated with HOMA-IR.
Conclusion
In this rural Chinese cohort, short sleep duration is independently associated with increased insulin resistance among women only, even after adjusting for adiposity and other potential confounders.
doi:10.1016/j.sleep.2011.04.006
PMCID: PMC3210935  PMID: 21940204
sleep duration; insulin resistance; adiposity; gender; rural; adults
12.  Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men 
Diabetes  2010;59(9):2126-2133.
OBJECTIVE
Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects of a drug, modafinil, that increases alertness during wakefulness.
RESEARCH DESIGN AND METHODS
This 12-day inpatient General Clinical Research Center study included 20 healthy men (age 20–35 years and BMI 20–30 kg/m2). Subjects spent 10 h/night in bed for ≥8 nights including three inpatient nights (sleep-replete condition), followed by 5 h/night in bed for 7 nights (sleep-restricted condition). Subjects received 300 mg/day modafinil or placebo during sleep restriction. Diet and activity were controlled. On the last 2 days of each condition, we assessed glucose metabolism by intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp. Salivary cortisol, 24-h urinary catecholamines, and neurobehavioral performance were measured.
RESULTS
IVGTT-derived insulin sensitivity was reduced by (means ± SD) 20 ± 24% after sleep restriction (P = 0.001), without significant alterations in the insulin secretory response. Similarly, insulin sensitivity assessed by clamp was reduced by 11 ± 5.5% (P < 0.04) after sleep restriction. Glucose tolerance and the disposition index were reduced by sleep restriction. These outcomes were not affected by modafinil treatment. Changes in insulin sensitivity did not correlate with changes in salivary cortisol (increase of 51 ± 8% with sleep restriction, P < 0.02), urinary catecholamines, or slow wave sleep.
CONCLUSIONS
Sleep restriction (5 h/night) for 1 week significantly reduces insulin sensitivity, raising concerns about effects of chronic insufficient sleep on disease processes associated with insulin resistance.
doi:10.2337/db09-0699
PMCID: PMC2927933  PMID: 20585000
13.  Sleep Deficiency and Sleep Health Problems in Chinese Adolescents 
A survey of sleep schedules, sleep health, and the impact on school performance was conducted in 585 adolescents in a high school in China. A high level of early and circadian-disadvantaged sleep/wake schedules during weekdays was observed. Significantly shorter sleep duration on weekdays was reported (P < 0.0001). Older teenagers slept significantly less than the younger teenagers (P < 0.0001). Complaints of inadequate sleep and sleepiness during weekdays were prevalent. Night awakenings were reported in 32.2% of students. Students with a sleep length of less than 7 hours, complaint of inadequate sleep, or excessive daytime sleepiness during weekdays were more likely to report an adverse effect of poor sleep on performance. The present observations are qualitatively similar to those reported in our study in American adolescents, particularly with respect to Chinese adolescents exhibiting a similar sleep deficiency on weekdays. We concluded that sleep deficiency and sleep health problems were prevalent in the participating adolescents in China, and were perceived to adversely affect school performance.
doi:10.4137/CMPed.S8407
PMCID: PMC3620771  PMID: 23641162
sleep deprivation; sleep health problem; adolescents; school performance
14.  Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults 
Background
The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization.
Objective
To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population.
Methods
The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs.
Results
Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%.
Conclusions
Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low.
Clinical Implications
Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed.
Capsule summary
Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low.
doi:10.1016/j.jaci.2008.08.009
PMCID: PMC2747487  PMID: 18805578
aeroallergens; rural; farming community; Chinese; food allergens; prevalence; sensitization; skin prick tests
15.  Delayed sleep phase syndrome in adolescents: prevalence and correlates in a large population based study 
BMC Public Health  2013;13:1163.
Background
The aims of this study were to estimate the prevalence of Delayed Sleep Phase Syndrome (DSPS) in adolescence, and to examine the association to insomnia and school non-attendance.
Methods
Data stem from a large population based study in Hordaland County in Norway conducted in 2012, the ung@hordaland study. In all, 10,220 adolescents aged 16–18 years (54% girls) provided self-reported data on a range of sleep parameters: DSPS was defined according to the International Classification of Sleep Disorders, Revised (ICSD-R) criteria, while insomnia was defined according to the Quantitative Criteria for Insomnia. Other sleep parameters included time in bed, sleep duration, sleep efficiency, oversleeping, sleep onset latency, wake after sleep onset, subjective sleep need, sleep deficiency, sleepiness and tiredness. Sleep data were calculated separately for weekdays and weekends. Data on school non-attendance were provided by official registers.
Results
The prevalence of DSPS was 3.3%, and significantly higher among girls (3.7%) than boys (2.7%). There was a strong overlap between DSPS and insomnia, with more than half of the adolescents with DSPS also meeting the criteria for insomnia (53.8% for boys and 57.1% for girls). Adolescents with DSPS had significantly higher odds ratios (OR) of non-attendance at school. After adjusting for sociodeographical factors, insomnia and depression, the adjusted ORs for days of non-attendance were OR = 3.22 (95% CI: 1.94-5.34) for boys and OR = 1.87 (95% CI: 1.25-2.80) for girls. A similar effect was found for hours of non-attendance for boys, with an adjusted OR = 3.05 (95% CI: 1.89-4.92). The effect for girls was no longer significant after full adjustment (OR =1.48 [95% CI: 0.94-2.32]).
Conclusions
This is one of the first studies to estimate the prevalence of DSPS in adolescents. The high prevalence of DSPS, and overlap with insomnia, in combination with the odds of school non-attendance, suggest that a broad and thorough clinical approach is warranted when adolescents present with symptoms of DSPS.
doi:10.1186/1471-2458-13-1163
PMCID: PMC3878844  PMID: 24330358
Delayes sleep phase syndrome; Sleep; Prevalence; Correlates; Epidemiology
16.  Role of sleep duration in the regulation of glucose metabolism and appetite 
Sleep curtailment has become a common behavior in modern society. This review summarizes the current laboratory evidence indicating that sleep loss may contribute to the pathophysiology of diabetes mellitus and obesity. Experimentally-induced sleep loss in healthy volunteers decreases insulin sensitivity without adequate compensation in beta-cell function, resulting in impaired glucose tolerance and increased diabetes risk. Lack of sleep also down-regulates the satiety hormone leptin, up-regulates the appetite-stimulating hormone ghrelin, and increases hunger and food intake. Taken together with the epidemiologic evidence for an association between short sleep and the prevalence or incidence of diabetes mellitus and/or obesity, these results support a role for reduced sleep duration in the current epidemic of these metabolic disorders. Screening for habitual sleep patterns in patients with “diabesity” is therefore of great importance. Studies are warranted to investigate the putative therapeutic impact of extending sleep in habitual short sleepers with metabolic disorders.
doi:10.1016/j.beem.2010.07.005
PMCID: PMC3018785  PMID: 21112019
Sleep deprivation; glucose metabolism; appetite regulation; diabetes; obesity
17.  Sleep Duration and Coronary Heart Disease Mortality Among Chinese Adults in Singapore: A Population-based Cohort Study 
American Journal of Epidemiology  2008;168(12):1367-1373.
While some studies have found a positive association between both short and long sleep durations and cardiovascular disease (CVD), others have found an association only with a long or short sleep duration. In addition, there are limited data from non-Western populations on this topic. The authors examined the association between sleep duration and coronary heart disease (CHD) mortality among Chinese adults in Singapore (1993–2006), performing a prospective cohort study among 58,044 participants aged ≥45 years (55.9% women) without preexisting CVD. The main outcome of interest was CHD mortality (n = 1,416). The authors found both short and long sleep durations to be positively associated with CHD mortality, independent of smoking, alcohol intake, and body mass index. Compared with persons with a sleep duration of 7 hours (referent), the multivariable relative risk of CHD mortality for a sleep duration of ≤5 hours was 1.57 (95% confidence interval: 1.32, 1.88); for a sleep duration of ≥9 hours, it was 1.79 (95% confidence interval: 1.48, 2.17). This association persisted in subgroup analyses by sex and body mass index. In a population-based cohort of Chinese adults from Singapore, sleep durations of ≤5 hours and ≥9 hours (versus 7 hours) were modestly associated with CHD mortality. These results suggest that sleep duration may be an important marker for CVD.
doi:10.1093/aje/kwn281
PMCID: PMC2643470  PMID: 18952563
Asian continental ancestry group; cardiovascular diseases; coronary disease; mortality; Singapore; sleep
18.  Sleep Duration and Coronary Heart Disease Mortality Among Chinese Adults in Singapore 
American journal of epidemiology  2008;168(12):1367-1373.
While some studies have found a positive association between both short and long sleep durations and cardiovascular disease (CVD), others have found an association only with a long or short sleep duration. In addition, there are limited data from non-Western populations on this topic. The authors examined the association between sleep duration and coronary heart disease (CHD) mortality among Chinese adults in Singapore (1993-2006), performing a prospective cohort study among 58,044 participants aged ≥45 years (55.9% women) without preexisting CVD. The main outcome of interest was CHD mortality (n = 1,416). The authors found both short and long sleep durations to be positively associated with CHD mortality, independent of smoking, alcohol intake, and body mass index. Compared with persons with a sleep duration of 7 hours (referent), the multivariable relative risk of CHD mortality for a sleep duration of ≤5 hours was 1.57 (95% confidence interval: 1.32, 1.88); for a sleep duration of ≥9 hours, it was 1.79 (95% confidence interval: 1.48, 2.17). This association persisted in subgroup analyses by sex sleep and body mass index. In a population-based cohort of Chinese adults from Singapore, sleep durations of ≤5 hours and ≥9 hours (versus 7 hours) were modestly associated with CHD mortality. These results suggest that duration may be an important marker for CVD.
doi:10.1093/aje/kwn281
PMCID: PMC2643470  PMID: 18952563
Asian continental ancestry group; cardiovascular diseases; coronary disease; mortality; Singapore; sleep
19.  Sleep facilitates long-term face adaptation 
Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as ‘storage’. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation—which are usually not considered to play a relevant role in mnemonic processes—with learning and memory, and at the same time reveal a new function of sleep in cognition.
doi:10.1098/rspb.2013.1698
PMCID: PMC3768314  PMID: 23986109
adaptation; sleep; learning; faces; figural after-effects; plasticity
20.  Influence of degree of specific allergic sensitivity on severity of rhinitis and asthma in Chinese allergic patients 
Respiratory Research  2011;12(1):95.
Background
The association between sensitizations and severity of allergic diseases is controversial.
Objective
This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitization in allergic patients in China.
Method
A cross-sectional survey was performed in 6304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire documenting their respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. Among the recruited subjects, 2268 provided blood samples for serum measurement of specific IgE (sIgE) against 16 common aeroallergens.
Results
Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was associated with the skin wheal size and the level of sIgE to Artemisia vulgaris and Ambrosia artemisifolia (p < 0.001). Moderate-severe asthma was associated with increasing wheal size and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (p < 0.001). Moderate-severe rhinitis and asthma were also associated with increase in number of positive skin prick test and sIgE.
Conclusions
Artemisia vulgaris and Ambrosia artemisifolia sensitizations are associated with the severity of intermittent rhinitis and D. pteronyssinus and D. farinae sensitizations are associated with increasing severity of asthma in China. Increase in number of allergens the patients are sensitized to may also increase the severity of rhinitis and asthma.
doi:10.1186/1465-9921-12-95
PMCID: PMC3145577  PMID: 21831329
sensitization; aeroallergens; disease severity; allergic rhinitis; asthma; association.
21.  211 Influence of Degree of Specific Allergic Sensitivity on Severity of Rhinitis and Asthma in Chinese Allergic Patients 
Background
The associations between sensitizations and severity of allergic diseases are controversial. This study was to investigate the association between severity of asthma and rhinitis and degree of specific allergic sensitivity in allergic patients in China.
Methods
A cross-sectional survey was performed in 6,304 patients with asthma and/or rhinitis from 4 regions of China. Patients completed a standardized questionnaire related to the respiratory and allergic symptoms, their impact on sleep, daily activities, school and work. They also underwent skin prick tests with 13 common aeroallergens. 2,268 of them were taken blood for serum specific IgE (sIgE) measurements for 16 common aeroallergens.
Results
Significantly higher percentage of patients with moderate-severe intermittent rhinitis were sensitized to outdoor allergens while percentage of patients sensitized to indoor allergens was increased with increasing severity of asthma. Moderate-severe intermittent rhinitis was related to skin wheal size and sIgE to Artemisia vulgaris and Ambrosia artemisifolia (P < 0.001). Moderate-severe asthma was associated with increasing in skin and sIgE response to Dermatophagoides (D.) pteronyssinus and D. farinae (P < 0.001). Moderate-severe rhinitis and asthma were also associated with increasing in number of skin and sIgE sensitized allergens.
Conclusions
Outdoor allergen sensitizations are significantly associated with severity of intermittent rhinitis and indoor allergen sensitizations are significantly associated with severity of asthma in patients in China. Number of allergen sensitization is also related to severity of rhinitis and asthma.
doi:10.1097/01.WOX.0000411968.40276.b5
PMCID: PMC3512821
22.  Shorter sleep may be a risk factor for impaired bone mass accrual in childhood 
The purpose of the study was to investigate whether sleep duration during early childhood was associated with fat mass and bone mineral content (BMC). BMC and fat mass were measured by dual-energy x-ray absorptiometry (DXA) in children (n=336) ages 4–12 years. Sleep was quantified according to parental report of hours slept at night and napping. The relationship between sleep pattern and body composition was tested using ANOVA including confounding factors. Based on the sample distribution, children were grouped into tertiles of sleep duration. BMC was greater in children with longer sleep duration (p=0.02). Age was inversely associated with sleep duration; therefore the sample was analyzed by age category using seven years old as the cut-point. The relationship remained significant only among younger children. Napping was positively associated with BMC (p=0.001). Sleep duration was not associated with fat parameters. Longer sleep duration, may allow for optimal energy resource partitioning in which bone is favored. Sleep duration of less than 8 hours may impair bone mass accrual, particularly during periods of rapid growth.
doi:10.1016/j.jocd.2011.06.005
PMCID: PMC3208825  PMID: 22051093
sleep curtailment; bone mineral content; growth; pediatric
23.  Adolescent Sleep, Risk Behaviors, and Depressive Symptoms: Are They Linked? 
Objective
To explore how weekday and weekend sleep patterns are related to adolescent substance use, depressive symptoms, and school truancy.
Methods
Self-report surveys of 242 youth (93.4% white, mean age 16.4 years).
Results
Longer weekday sleep duration was inversely associated with depressive symptoms, past month alcohol use, and drunkenness. Later weekend bedtime and wake-times, compared to those of weekdays, were associated with increased substance use and truancy.
Conclusions
Weekday sleep duration appears to be protective for substance use, depression and school truancy for teenagers. However, inconsistent sleep patterns between weekdays and weekends were associated with a range of markers for adolescent risk.
PMCID: PMC3086400  PMID: 19814603
adolescents; sleep; risk behaviors; depressive symptoms
24.  Self-reported Sleep Complaints With Long and Short Sleep: A Nationally Representative Sample 
Psychosomatic medicine  2004;66(2):239-241.
Objective
Although the problems associated with insufficient sleep have been thoroughly researched, there has been far less substantiation of problems associated with long sleep. Recent evidence shows that habitual sleep duration greater than 7 hours is associated with increased rates of mortality. This study compared the rates of sleep problems in both long and short sleepers.
Methods
Self-reported sleep complaints (eg, sleep onset latency, awakenings during the night, early morning awakenings, nonrestorative sleep, and daytime sleepiness) of nearly 1000 adults who participated in the National Sleep Foundation’s 2001 Sleep in America Poll, were compared with reported hours of weekday sleep.
Results
There are U-shaped relationships of sleep complaints with reported weekday total sleep time. More specifically, 8-hour sleepers reported less frequent symptoms than long sleepers or 7-hour sleepers.
Conclusions
Thus, long sleepers, as well as short sleepers, report sleep problems, focusing attention to the often-overlooked problems of the long sleeper.
PMCID: PMC3687531  PMID: 15039509
sleep; sleep disorders; Long Sleeper Syndrome; Short Sleeper Syndrome; insomnia
25.  Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway 
Background
Sleepiness and cognitive dysfunction are recognized as prominent consequences of sleep deprivation. Experimentally induced short-term sleep fragmentation, even in the absence of any reductions in total sleep duration, will lead to the emergence of excessive daytime sleepiness and cognitive impairments in humans. Tumor necrosis factor (TNF)-α has important regulatory effects on sleep, and seems to play a role in the occurrence of excessive daytime sleepiness in children who have disrupted sleep as a result of obstructive sleep apnea, a condition associated with prominent sleep fragmentation. The aim of this study was to examine role of the TNF-α pathway after long-term sleep fragmentation in mice.
Methods
The effect of chronic sleep fragmentation during the sleep-predominant period on sleep architecture, sleep latency, cognitive function, behavior, and inflammatory markers was assessed in C57BL/6 J and in mice lacking the TNF-α receptor (double knockout mice). In addition, we also assessed the above parameters in C57BL/6 J mice after injection of a TNF-α neutralizing antibody.
Results
Mice subjected to chronic sleep fragmentation had preserved sleep duration, sleep state distribution, and cumulative delta frequency power, but also exhibited excessive sleepiness, altered cognitive abilities and mood correlates, reduced cyclic AMP response element-binding protein phosphorylation and transcriptional activity, and increased phosphodiesterase-4 expression, in the absence of AMP kinase-α phosphorylation and ATP changes. Selective increases in cortical expression of TNF-α primarily circumscribed to neurons emerged. Consequently, sleepiness and cognitive dysfunction were absent in TNF-α double receptor knockout mice subjected to sleep fragmentation, and similarly, treatment with a TNF-α neutralizing antibody abrogated sleep fragmentation-induced learning deficits and increases in sleep propensity.
Conclusions
Taken together, our findings show that recurrent arousals during sleep, as happens during sleep apnea, induce excessive sleepiness via activation of inflammatory mechanisms, and more specifically TNF-α-dependent pathways, despite preserved sleep duration.
doi:10.1186/1742-2094-9-91
PMCID: PMC3411474  PMID: 22578011
TNF-α; Sleep fragmentation; Neurocognitive impairments; Sleep apnea; ATP

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