Subjective health perception in healthy young men changes in response to experimentally restricted sleep and subsequent recovery sleep.

Sleep and subjective health are both prospectively related to objective indices of health and health care use. Here, we tested whether five days with restricted sleep and subsequent recovery days affect subjective health and is related to increased levels of circulating IL-6 and TNF-α and fatigue. Nine healthy men (23-28 ears) went through a 6-week sleep protocol with subjects as their own controls in a repeated measures design with a total of 11 nights in a sleep laboratory. The experimental part of the protocol included three baseline days (sleep 23-07 h), five days with sleep restriction (03-07 h) and three recovery days (23-07 h) in the sleep laboratory. Subjective health and fatigue was recorded daily. Eight blood samples were drawn each day (every third hour) on 8 days of the protocol and analyzed with respect to IL-6 and TNF-α. Subjective health deteriorated gradually during restricted sleep (p=.002) and returned to baseline levels after three days of recovery. IL-6 and TNF-α did not change significantly. Fatigue increased gradually during sleep restriction (p=.001), which significantly contributed to the association between restricted sleep and subjective health. The study is the first to show that subjective health is directly responsive to changes in sleep length and related to increased fatigue. Thus, subjective health is differently appraised after manipulation of one of its presumed determinants. Larger experimental studies would be beneficial to further distinguish causation from association regarding the underpinnings of subjective health.

Inflammation and positive affect are associated with subjective health in women of the general population.

Poor subjective health has been associated with higher levels of inflammatory cytokines. We investigated whether such an association would apply to women of the general population. Levels of cytokines, affect and subjective health were assessed in 347 women of the general population aged 45 to 90 years. Higher levels of interleukin-6 were associated with poor subjective health, especially in participants over 65 years of age. Positive affect was a more robust determinant of subjective health than negative affect. The presence of low-grade inflammation and absence of positive affect, rather than presence of negative affect, may be important determinants of subjective health.

Leptin and adiponectin: distribution and associations with cardiovascular risk factors in men and women of the general population.

OBJECTIVE: In view of the increasing prevalence of obesity worldwide, understanding the role of the recently discovered adipokines leptin and adiponectin is of high clinical relevance. The aim of the present study was to assess the association between levels of leptin and adiponectin with age, known cardiovascular risk factors and to establish whether there are differences between men and women of the general population. METHODS: A total of 98 men and 107 women of the general population, aged between 20 and 74 years, underwent a medical examination at a clinical research center and fasting morning blood samples were also taken. RESULTS: Leptin (mean 7.5 µg l(-1) in men and 16.0 µg l(-1) in women) and adiponectin (mean 7.3 mg l(-1) in men and 11.9 mg l(-1) in women) levels were higher in women than men (Ps < 0.001). Both leptin and adiponectin levels increased with advancing age in both men and women (Ps < 0.05). Leptin was highly associated with factors for metabolic syndrome in men while in women, leptin was highly associated with inflammatory factors. Adiponectin was associated with blood lipids in both men and women, and glucose homeostasis more in women than in men. CONCLUSIONS: Leptin and adiponectin levels were ∼2 times and 1.5 times higher in women than in men, respectively. In addition, although leptin and adiponectin were associated to CVD risk factors in both men and women, we observed differences in specific CVD risk factor groups between men and women. These differences may be due to different regulatory mechanisms and effects of these adipokines in men and women.

Association of TNFSF15 polymorphism with irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is the most common gastrointestinal disorder, affecting more than 10% of the general population worldwide. Although a genetic component is suspected, unambiguous susceptibility genes have so far not been identified. This study tested the hypothesis that genes contributing to epithelial barrier integrity, control of mucosal immune responses and interactions with bacteria in the gut are associated with IBS. METHODS: Single nucleotide polymorphisms (SNPs) corresponding to top signals of association with Crohn's disease at 30 known susceptibility loci were tested for their effect on IBS risk in 1992 individuals from two independent case-control cohorts from Sweden and the USA. Association tests included a conservative Bonferroni correction for multiple comparisons, and were also performed on specific subgroups of patients characterised by constipation (IBS-C), diarrhoea (IBS-D) or alternating constipation and diarrhoea (IBS-A). RESULTS: The Crohn's disease risk allele rs4263839 G in the TNFSF15 gene was significantly associated with an increased risk of both IBS (p=2.2×10(-5); OR 1.37) and more pronouncedly, IBS-C (p=8.7×10(-7); OR 1.79) in the entire sample. Similar associations and risk effects of the same magnitude were observed in the two cohorts analysed separately. A correlation between rs4263839 genotype and TNFSF15 mRNA expression was detected both in peripheral blood and in rectal mucosal biopsies from healthy individuals (combined p=0.0033). CONCLUSIONS: TNFSF15 is a susceptibility gene for IBS and IBS constipation. As TL1A, the protein encoded by TNFSF15, contributes to the modulation of inflammatory responses, the results support a role of immune activation in IBS.

Cytokines and memory across the mature life span of women.

Increasing evidence suggests a role of the immune system in modulation of cognition, but details on affected memory systems are largely lacking. We therefore aimed to study the relation between selected cytokines and subsets of memory, and the impact of age in these relations. From a random population-based sample (the Betula Prospective Cohort Study), 298 women (age 45-90) were studied in terms of episodic recall and recognition, semantic fluency and knowledge, and prospective memory. Circulating cytokines of relevance for cognition and aging were measured with ELISA. Levels of interleukin (IL)-6 and sIL-2R were significantly and negatively associated with most cognitive variables, while the opposite was true for IL-1ß. Age shared substantial variance with both cytokines and memory, and turned most correlations non-significant when controlled for together with education, BMI and presence of disease. Interactions between age and cytokines were further analyzed in multiple regressions. For IL-6, significant negative interactions with age were found for semantic fluency (p<0.05) and prospective memory (p<0.01), and for sIL-2R in predicting semantic knowledge (p<0.05), indicating an increased negative impact of these cytokines on memory with increasing age. In conclusion, the study indicates a relation between cytokines and memory that appears to be largely mediated by age, and supports the suggestion that cytokine dysregulation with higher age may interact with cognitive aging.

Prospective diary evaluation of unexplained abdominal pain and bowel dysfunction: a population-based colonoscopy study.

INTRODUCTION: Diagnostic criteria for irritable bowel syndrome (IBS) have not been validated by prospective symptom diary. We investigated the bowel patterns in community subjects with and without non-organic abdominal pain, and compared the symptoms with subjects fulfilling the Rome II criteria (IBS). METHODS: From the Swedish population register, a random sample completed an abdominal symptom questionnaire. Responders were subsequently invited for a clinical evaluation and offered a colonoscopy regardless of whether they had abdominal symptoms or not. A total of 268 subjects underwent colonoscopy, clinical evaluation by gastroenterologist, laboratory investigations, and completed the Rome questionnaire and prospective gastrointestinal (GI) symptom diaries for 1 week. Twenty-three subjects of 268 were excluded due to organic GI disease. RESULTS: Subjects recorded 2,194 bowel movements and 370 abdominal pain episodes on 1,504 days. Subjects with pain in the diary (n = 81) had higher stool frequency (P = 0.01), more urgency (P = 0.0002), feelings of incomplete evacuation (P = 0.0002), nausea (P = 0.0009), and abdominal bloating (P = 0.0005) than subjects without pain (n = 151). Twenty-eight subjects (12%) fulfilled the Rome II criteria for IBS. Together, they had 96 pain episodes but only 4% were improved by defecation; 29% of the pain episodes started or worsened after a meal. Subjects with IBS and other subjects with non-organic abdominal pain (n = 64) exhibited no differences in terms of the proportions of pain episodes improved by defecation, bloating, stool frequency, consistency, or defecatory symptoms. CONCLUSIONS: Current criteria for IBS that rely on recall of the relationship between abdominal pain and bowel disturbance may overcall this association when measured prospectively.