| 1. |
- Peden, John F., et al.
(författare)
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A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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| 2. |
- Andreasson, Anna N., et al.
(författare)
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Development and preliminary validation of the Sickness Questionnaire (SicknessQ)
- 2013
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 32
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Tidskriftsartikel (refereegranskat)abstract
- The lack of questionnaires to measure subjective feelings of being sick made us develope the Sickness Questionnaire (SicknessQ) for assessment of sickness behavior in people. The objective of the present investigation was to test its internal consistency, criteria validity, and sensitivity to capture the sickness response in an experimental setting. An initial pool of items was developed based on previous research. The statistical properties of SicknessQ was assessed in 172 men and women primary care patients with acute complaints and involved three steps: (1) principal component analyses to reduce the number of items and to identify latent factor structures, (2) tests of internal consistencies of subscales, and (3) hierarchical regression analyses to test criteria validity of the subscales. Subsequently, sensitivity to change was tested in a placebo controlled experiment in which 31 blinded healthy men and women were injected with endotoxin (LPS) to provoke sickness behavior. Principal components analysis suggested a 3-factor solution with a total of 11 items measuring fatigue (5 items), pain (4 items) and emotion (2 items). The total scale as well as each of the three separate factors were significantly changed 90 min after endotoxin injection as compared to baseline (p’s < .01). In all, the new 11-item SicknessQ is highly sensitive to a mild systemic inflammation. Further studies are planned to test its usefulness and prognostic value in clinical settings.
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| 3. |
- Axelsson, John, et al.
(författare)
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Beauty sleep : experimental study on the perceived health and attractiveness of sleep deprived people
- 2010
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Ingår i: The BMJ. - : BMJ. - 1756-1833. ; 341
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Tidskriftsartikel (refereegranskat)abstract
- Our findings show that sleep deprived people appear less healthy, less attractive, and more tired compared with when they are well rested. This suggests that humans are sensitive to sleep related facial cues, with potential implications for social and clinical judgments and behaviour. Studies are warranted for understanding how these effects may affect clinical decision making and can add knowledge with direct implications in a medical context.
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| 4. |
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| 5. |
- Axelsson, John, et al.
(författare)
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Effects of Sustained Sleep Restriction on Mitogen-Stimulated Cytokines, Chemokines and T Helper 1/T Helper 2 Balance in Humans
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. Methods: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00 - 07.00 h) followed by 5 days with restricted sleep (03.00 - 07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-alpha), interleukin (IL) -1 beta, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed. Results: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-alpha and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day. Conclusions: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences. BAS AK, 1991, IMMUNOLOGICAL REVIEWS, V123, P5
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| 6. |
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| 7. |
- Axelsson, Linn, 1977-
(författare)
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Making Borders : Engaging the threat of Chinese textiles in Ghana
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The borders of the twenty-first century come in many forms and are performed by an increasing number of actors in a broad variety of places, both within and beyond the territories of nation-states. This thesis sets out a detailed political geography of how borders operate to reconcile the often conflicting demands of open markets and security. Focusing on Ghana, where there is a widespread fear that the inflow of Chinese versions of African prints will lead to the collapse of the local textile industry, the study explores where and when borders are enforced, who performs them and what kinds of borders are enacted in order to maintain and protect the Ghanaian nation and market without compromising the country’s status as a liberal economy. It combines interviews and documentary sources with analysis drawn from border, security and migration studies to explore three sets of spatial strategies that have defined the Ghanaian approach to the perceived threat of Chinese African prints. They are the institution of a single corridor for African print imports, the anti-counterfeiting raids carried out in Ghana’s marketplaces, and the promotion of garments made from locally produced textiles as office wear through the National Friday Wear and Everyday Wear programmes. These strategies stretch, disperse and embody the borders of the state or nation to control trade in ways that resolve the fears of both open flows and closed borders. This thesis thus seeks to show how a geographical analysis can clarify the specificities of how borders now work to control mobility. In doing so, it not only unsettles conventional assumptions about what borders are and where they are supposed to be located, but also the idea that borders primarily are used to constrain the mobility of certain people while facilitating economic flows. Furthermore, this thesis adds to the understanding of the variety of responses to the inflow of Chinese consumer products to the African continent.
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| 8. |
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| 9. |
- Eapen, Valsamma, et al.
(författare)
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"Are you available for the next 18 months?" - methods and aims of a longitudinal birth cohort study investigating a universal developmental surveillance program: the ’Watch Me Grow’ study
- 2014
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 14, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Universal developmental surveillance programs aimed at early identification and targeted early intervention significantly improve short-and long-term outcomes in children at risk of developmental disorders. However, a significant challenge remains in providing sufficiently rigorous research and robust evidence to inform policy and service delivery. This paper describes the methods of the ’Watch Me Grow’ study that aims to maximise accurate early detection of children with developmental disorders through a partnership formed between policy makers, service providers and researchers. Methods/Design: A mixed methods study design was developed consisting of: (1) a qualitative study of parents and health service providers to investigate barriers and enablers of developmental surveillance; (2) recruitment of a birth cohort and their longitudinal follow-up to 18 months of age to: a) assess risk factors for not accessing existing developmental surveillance programs and b) estimate the prevalence of children identified with developmental risk; (3) comparison of surveillance outcomes with a reference standard at 18 months of age to assess the diagnostic test accuracy of existing and alternative developmental surveillance tools; and (4) comparison of developmental surveillance models to inform policy recommendations. Data linkage will be used to determine the uptake and representativeness of the study participant group versus non-participants. Discussion: The Watch Me Grow study is expected to provide a collaborative opportunity to enhance universal developmental surveillance for early accurate identification of developmental risk. This will also provide quality evidence about identification of developmental risk and access to services to be embedded in existing practice with linkages to policy development.
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| 10. |
- Fondell, Elinor, et al.
(författare)
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Short natural sleep is associated with higher T cell and lower NK cell activities
- 2011
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 25:7, s. 1367-1375
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Tidskriftsartikel (refereegranskat)abstract
- Short sleep duration increases the risk of several diseases, possibly involving compromised immune function. However, most previous studies are based on experimentally induced sleep deprivation, and only a few have studied natural variations in sleep duration. Thus our aim was to study how natural variations in sleep duration affect immune function. In total, 36 healthy men and women, aged 20-54, donated blood; 29 on three consecutive mornings, and seven on one morning. Each morning, participants self-reported sleep duration the night prior to blood draw. General sleep patterns, physical activity and stress were also assessed. A flow-cytometric assay was used to measure natural killer cell activity (NKCA), T cell function (in response to PHA, influenza, and SEA+B), and B cell function (in response to PWM) per volume whole blood. Short sleep duration prior to blood draw (<7h) was associated with 49% higher PHA-induced T cell function (95% CI 7/109%) and 30% lower NKCA compared with normal prior sleep (7-9h) (95% CI -46/-8%). In addition, high perceived stress was associated with 39% higher PHA-induced T cell function (95% CI 0/94%). High general physical activity was associated with 47% increased numbers of B cells and 28% increased numbers of T cells, but not with immune function. Our results suggest strong relationships between short sleep duration and T- and NK-cell functions. The stability of the findings as well as the clinical consequences of the link between short sleep and immune function should be explored in future studies.
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| 11. |
- Jernelöv, S., et al.
(författare)
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Development of atopic disease and disturbed sleep in childhood and adolescence : a longitudinal population-based study
- 2013
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Ingår i: Clinical and Experimental Allergy. - : Wiley-Blackwell. - 0954-7894 .- 1365-2222. ; 43:5, s. 552-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Both atopic diseases and sleep disturbances have increased during recent decades, especially in children. Sleep is important for many aspects of immune regulation relevant in allergic diseases, and sleep disturbances are common in patients with such diseases. A connection between sleep disturbances and fatigue, and atopic disease is well established. However, the time course and putative causal relationships between these factors are obscure.OBJECTIVE: We aimed at investigating the developmental relationships between subjectively reported sleep disturbances and symptoms of atopic disease, from childhood to adolescence.METHODS: This longitudinal study used parent-report questionnaire data on symptoms of atopic disease, and sleep disturbances, from the Twin Study of Child and Adolescent Development (TCHAD). Overall, 1480 twin pairs born in Sweden were approached first when children were 8-9 years old, and again later at 13-14 years old. Response rates were 75% and 72%. Data from the TCHAD questionnaires were linked to the Swedish Medical Birth Register based on personal identification numbers.RESULTS: Being overtired at age 8 increased the risk [OR; 95% CI (2.59; 1.31-5.11)] to develop rhinitis symptoms at age 13, even when controlling for gender, previous rhinitis, Socio-economic status, birth weight and other sleep disturbances at age 8. Likewise, symptoms of asthma at age 8 was an independent risk factor for being overtired at age 13 [OR; 95% CI (2.64; 1.44-4.84)], controlling for similar confounders.CONCLUSION & CLINICAL RELEVANCE: The findings from this study are consonant with the proposition that atopic disease and disturbed sleep are more than passively interrelated. Future research needs to delineate whether causal relationships between these problems are at hand and, if so, at what periods in development this applies. These results point to a need for clinicians to investigate sleep difficulties and treat impaired sleep in paediatric patients with atopic disease.
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| 12. |
- Jernelöv, Susanna, et al.
(författare)
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Efficacy of a behavioral self-help treatment with or without therapist guidance for co-morbid and primary insomnia - a randomized controlled trial
- 2012
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Ingår i: BMC Psychiatry. - 1471-244X. ; :12
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCognitive behavioral therapy is treatment of choice for insomnia, but availability is scarce. Self-help can increase availability at low cost, but evidence for its efficacy is limited, especially for the typical insomnia patient with co-morbid problems. We hypothesized that a cognitive behaviorally based self-help book is effective to treat insomnia in individuals, also with co-morbid problems, and that the effect is enhanced by adding brief therapist telephone support.MethodsVolunteer sample; 133 media-recruited adults with insomnia. History of sleep difficulties (mean [SD]) 11.8 [12.0] years. 92.5% had co-morbid problems (e.g. allergy, pain, and depression). Parallel randomized (block-randomization, n ≥ 21) controlled "open label" trial; three groups-bibliotherapy with (n = 44) and without (n = 45) therapist support, and waiting list control (n = 44). Assessments before and after treatment, and at three-month follow-up. Intervention was six weeks of bibliotherapeutic self-help, with established cognitive behavioral methods including sleep restriction, stimulus control, and cognitive restructuring. Therapist support was a 15-minute structured telephone call scheduled weekly. Main outcome measures were sleep diary data, and the Insomnia Severity Index.ResultsIntention-to-treat analyses of 133 participants showed significant improvements in both self-help groups from pre to post treatment compared to waiting list. For example, treatment with and without support gave shorter sleep onset latency (improvement minutes [95% Confidence Interval], 35.4 [24.2 to 46.6], and 20.6 [10.6 to 30.6] respectively), and support gave a higher remission rate (defined as ISI score below 8; 61.4%), than bibliotherapy alone (24.4%, p's < .001). Improvements were not seen in the control group (sleep onset latency 4.6 minutes shorter [-1.5 to 10.7], and remission rate 2.3%). Self-help groups maintained gains at three-month follow-up.ConclusionsParticipants receiving self-help for insomnia benefited markedly. Self-help, especially if therapist-supported, has considerable potential to be as effective as individual treatment at lower cost, also for individuals with co-morbid problems.
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| 13. |
- Jiao, Hong, et al.
(författare)
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Genetic Association and Gene Expression Analysis Identify FGFR1 as a New Susceptibility Gene for Human Obesity
- 2011
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 96:6, s. E962-E966
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Tidskriftsartikel (refereegranskat)abstract
- Context: Previous studies suggest a role for fibroblast growth factor receptor 1 (FGFR1) in the regulation of energy balance. Objective: Our objective was to investigate whether FGFR1 is an obesity gene by genetic association and functional studies. Design: The study was designed to genotype common FGFR1 single-nucleotide polymorphisms (SNP) in large cohorts, confirm significant results in additional cohorts, and measure FGFR1 expression in human adipose tissue and in rodent hypothalamus. Setting: General community and referral centers for specialized care was the setting for the study. Participants: We genotyped FGFR1 SNP in 2438 obese and 2115 lean adults and 985 obese and 532 population-based children. Results were confirmed in 928 obese and 2738 population-based adults and 487 obese and 441 lean children. Abdominal sc adipose tissue was investigated in 202 subjects. We also investigated diet-induced, obese fasting, and fed rats. Main Outcome Measures: We analyzed the association between FGFR1 SNP and obesity. In secondary analyses, we related adipose FGFR1 expression to genotype, obesity, and degree of fat cell differentiation and related hypothalamic FGFR1 to energy balance. Results: FGFR1 rs7012413*T was nominally associated with obesity in all four cohorts; metaanalysis odds ratio = 1.17 (95% confidence interval = 1.10-1.25), and P = 1.8 x 10(-6), which was P = 7.0 x 10(-8) in the recessive model. rs7012413*T was associated with FGFR1 expression in adipose tissue (P < 0.0001). In this organ, but not in skeletal muscle, FGFR1 mRNA (P < 0.0001) and protein (P < 0.05) were increased in obesity. In rats, hypothalamic expression of FGFR1 declined after fasting (P < ]0.001) and increased after diet-induced obesity (P < 0.05). Conclusions: FGFR1 is a novel obesity gene that may promote obesity by influencing adipose tissue and the hypothalamic control of appetite.
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| 14. |
- Karshikoff, B., et al.
(författare)
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Modality and sex differences in pain sensitivity during human endotoxemia
- 2014
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 46, s. 35-43
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Tidskriftsartikel (refereegranskat)abstract
- Systemic inflammation can induce pain hypersensitivity in animal and human experimental models, and has been proposed to be central in clinical pain conditions. Women are overrepresented in many chronic pain conditions, but experimental studies on sex differences in pain regulation during systemic inflammation are still scarce. In two randomized and double blind placebo controlled experiments, we used low doses of lipopolysaccharide (LPS) as an experimental model of systemic inflammation. The first study employed 0.8ng/kg LPS in a within-subject design of 8 individuals (1 woman), and the second study 0.6ng/kg LPS in a between-subject design of 52 participants (29 women). We investigated the effect on (a) pressure, heat, and cold pain thresholds, (b) suprathreshold noxious heat and cold sensitivity, and (c) conditioned pain modulation (CPM), and differences between men and women. LPS induced significantly lower pressure pain thresholds as compared to placebo (mean change with the 0.8ng/kg dose being -64±30kPa P=.04; with the 0.6ng/kg dose -58±55kPa, P<.01, compared to before injection), whereas heat and cold pain thresholds remained unaffected (P's>.70). Suprathreshold noxious pain was not affected by LPS in men (P's⩾.15). However, LPS made women rated suprathreshold noxious heat stimuli as more painful (P=.01), and showed a tendency to rate noxious cold pain as more painful (P=.06) as compared to placebo. Furthermore, LPS impaired conditioned pain modulation, a measure of endogenous pain inhibition, but this effect was also restricted to women (P<.01, for men P=.27). Pain sensitivity correlated positively with plasma IL-6 and IL-8 levels. The results show that inflammation more strongly affects deep pain, rather than cutaneous pain, and suggest that women's pain perception and modulation is more sensitive to immune activation than men's.
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| 15. |
- Kecklund, Göran, et al.
(författare)
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20th International Symposium on Shiftwork and Working Time : Biological Mechanisms, Recovery, and Risk Management in the 24-h Society
- 2012
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Ingår i: Chronobiology International. - : Informa UK Limited. - 0742-0528 .- 1525-6073. ; 29:5, s. 531-536
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Tidskriftsartikel (refereegranskat)abstract
- This dedicated issue of Chronobiology International is devoted to the selected proceedings of the 20th International Symposium on Shift Work and Working Time held in Stockholm, Sweden, 28 June to 1 July 2011. It constitutes the fifth such issue of the journal since 2004 dedicated to the selected proceedings to the meetings of the Working Time Society. The key theme of the 20th Symposium was "Biological Mechanisms, Recovery, and Risk Management in the 24-h Society." The collection of papers of this dedicated issue represents the best of contemporary research on the effects of night and rotating shift schedules on worker health and safety. The contents cover such topics as sleep restriction, injuries, health, and performance of night work and rotating shiftwork, plus light treatment as a countermeasure against the circadian disruption of shiftwork. The majority of the papers are observational field studies, including some of large sample size, and three studies are well-designed laboratory experiments. (Author correspondence: goran.kecklund@stress.su.se ).
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| 16. |
- Lidberg, Lisa, et al.
(författare)
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Self-rated health in response to experimental manipulations of inflammation is mediated by sickness behavior as assessed by the sickness questionnaire
- 2013
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Ingår i: Brain, Behavior, and Immunity. - : Elsevier BV. - 0889-1591. ; 32:Supplement, s. e34-e34
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Tidskriftsartikel (refereegranskat)abstract
- Factors that influence subjective health ratings (e.g. pain, tiredness, lack of energy) resemble immune activated sickness behavior. Accordingly, previous research has shown a relation between inflammatory cytokines and poor self-rated health. However, neither the causality of the association, nor what mediates it, is clear. In this study we investigated if a transient immune activation would affect subjective health perception and, if so, if this effect is mediated by symptoms of sickness behavior. Using a between-subject design, 51 healthy subjects were injected with either endotoxin (LPS 0.6 ng/kg) or placebo. Stimulation resulted in a peak response in pro-inflammatory cytokines after 90–120 min. Ninety minutes after injection, both perceived health framed to represent current (“How is your health right now?”) and global health (“How would you rate your general state of health”?) was significantly lower in the endotoxin condition (p’s < .01). The effect of endotoxin on self-rated health was mediated by sickness behavior as assessed by a newly developed questionnaire, Sickness Questionnaire, to 91% for current and 68 % for global health. In conclusion, it is demonstrated that a transient inflammatory activation, likely working through symptoms of sickness behavior, affects both subjectively perceived health for the moment as well as how health status on the more general level is appraised.
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| 17. |
- Moore, Derek G, et al.
(författare)
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During pregnancy, recreational drug-using women stop taking ecstasy (3,4-methylenedioxy-N-methylamphetamine) and reduce alcohol consumption, but continue to smoke tobacco and cannabis: initial findings from the Development and Infancy Study
- 2010
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Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 24, s. 1403-1410
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Tidskriftsartikel (refereegranskat)abstract
- While recreational drug use in UK women is prevalent, to date there is little prospective data on patterns of drug use in recreational drug-using women immediately before and during pregnancy. A total of 121 participants from a wide range of backgrounds were recruited to take part in the longitudinal Development and Infancy Study (DAISY) study of prenatal drug use and outcomes. Eighty-six of the women were interviewed prospectively while pregnant and/or soon after their infant was born. Participants reported on use immediately before and during pregnancy and on use over their lifetime. Levels of lifetime drug use of the women recruited were high, with women reporting having used at least four different illegal drugs over their lifetime. Most users of cocaine, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and other stimulants stopped using these by the second trimester and levels of use were low. However, in pregnancy, 64% of the sample continued to use alcohol, 46% tobacco and 48% cannabis. While the level of alcohol use reduced substantially, average tobacco and cannabis levels tended to be sustained at pre-pregnancy levels even into the third trimester (50 cigarettes and/or 11 joints per week). In sum, while the use of ‘party drugs’ and alcohol seems to reduce, levels of tobacco and cannabis use are likely to be sustained throughout pregnancy. The data provide polydrug profiles that can form the basis for the development of more realistic animal models.
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| 18. |
- Nilsonne, Gustav, et al.
(författare)
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Learning in a simple biological system : a pilot study of classical conditioning of human macrophages in vitro
- 2011
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Ingår i: Behavioral and Brain Functions. - : Springer Science and Business Media LLC. - 1744-9081. ; 7, s. 47-
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be performed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro. In macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with streptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation, conditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in the learning phase (p's < .05), regardless whether they received the conditioned stimulus or not at evocation. However, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If further experiments confirm that simple learning can occur in immune cells, this may have bearings not only on immune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly, whether capacities for simple learning in single cells extend beyond habituation, and how this would be demonstrated, remain open questions.
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| 19. |
- Olsson, Mats J., et al.
(författare)
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The Scent of Disease : Human Body Odor Contains an Early Chemosensory Cue of Sickness
- 2014
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Ingår i: Psychological Science. - : SAGE Publications. - 0956-7976 .- 1467-9280. ; 25:3, s. 817-823
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Tidskriftsartikel (refereegranskat)abstract
- Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals' level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a "behavioral immune response" that protects healthy individuals from sick ones by altering patterns of interpersonal contact.
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| 20. |
- Paré, Guillaume, et al.
(författare)
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Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding
- 2013
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 127:13, s. 1404-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundFixed-dose unmonitored treatment with dabigatran etexilate is effective and has a favorable safety profile in prevention of stroke in atrial fibrillation patients compared to warfarin. We hypothesized that genetic variants could contribute to inter-individual variability in blood concentrations of the active metabolite of dabigatran etexilate, and influence the safety and efficacy of dabigatran.Methods and ResultsWe successfully conducted a genome-wide association study in 2,944 RE-LY participants. The CES1 SNP rs2244613 was associated with trough concentrations, and the ABCB1 SNP rs4148738 and CES1 SNP rs8192935 were associated with peak concentrations at genome-wide significance (P<9 x 10-8) with a gene-dose effect. Each minor allele of the CES1 SNP rs2244613 was associated with lower trough concentrations (15% decrease per allele, 95%CI 10-19%; P=1.2 x 10-8) and a lower risk of any bleeding (OR=0.67, 95%CI 0.55-0.82; P=7 x 10-5) in dabigatran-treated participants, with a consistent but non-significant lower risk of major bleeding (OR=0.66, 95%CI 0.43-1.01). The interaction between treatment (warfarin versus all dabigatran) and carrier status was statistically significant (P=0.002) with carriers having less bleeding with dabigatran than warfarin (HR=0.59, 95%CI 0.46-0.76; P=5.2 x 10-5) in contrast to no difference in noncarriers (HR=0.96, 95%CI 0.81-1.14; P=0.65). There was no association with ischemic events, and neither rs4148738 nor rs8192935 was associated with bleeding or ischemic events.ConclusionsGenome-wide association analysis identified that carriage of CES1 rs2244613 minor allele occurred in 32.8% of patients in RELY and was associated with lower exposure to active dabigatran metabolite. The presence of the polymorphism was associated with a lower risk of bleeding.
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| 21. |
- Rehman, Javaid-ur, et al.
(författare)
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Sleeping during the day : effects on the 24-h patterns of IGF-binding protein 1, insulin, glucose, cortisol, and growth hormone.
- 2010
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 163:3, s. 383-90
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Disturbed sleep is a major risk factor for metabolic disturbances, including type 2 diabetes, but the involved mechanisms are still poorly understood. We investigated how an acute shift of sleep to the daytime affected IGF-binding protein 1 (IGFBP1), which is a risk factor for diabetes. METHODS: Seven healthy men (age, 22-32 years) participated in a night sleep condition (sleep 2300-0700 h) and a day sleep condition (0700-1500 h) with hourly blood samples taken for 25 h (starting at 1900 h) and isocaloric meals every 4th hour awake. The blood samples were analyzed for IGFBP1, insulin, GH, glucose, and cortisol. RESULT: The acute shift of sleep and meal timing (to 8 h) shifted the 24-h patterns of IGFBP1, glucose, insulin, and GH to a similar degree. However, the day sleep condition also resulted in elevated levels of IGFBP1 (area under curve (AUC)+22%, P<0.05), and reduced glucose levels (AUC-7%, P<0.05) compared with nocturnal sleep. Sleeping during the day resulted in elevated cortisol levels during early sleep and reduced levels in late sleep, but also in increased levels the subsequent evening (P's<0.05). CONCLUSION: Sleep-fasting seems to be the primary cause for the elevation of IGFBP1, irrespective of sleep timing. However, sleeping during the day resulted in higher levels of IGFBP1 than nocturnal sleep, suggesting altered metabolism among healthy individuals, which may have implications for other groups with altered sleep/eating habits such as shift workers. Moreover, sleep and meal times should be accounted for while interpreting IGFBP1 samples.
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| 22. |
- Ridefelt, Peter, et al.
(författare)
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Diurnal variability of total calcium during normal sleep and after an acute shift of sleep
- 2012
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 50:1, s. 147-151
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum total calcium is becoming a widely used test when screening for hyperparathyroidism (HPT) and other causes of hypercalcemia, even if serum calcium is tightly regulated in the body it is unclear whether the reference values are correct for tests taken at different times of the day or for individuals with altered sleep patterns. Thus, the aim was to investigate how timing of testing and sleep affects serum calcium. Methods: The diurnal variation of total calcium in serum during night-time and day-time conditions was studied in seven healthy volunteers. Serum samples for calcium measurements were collected every hour (48 samples per individual) to evaluate the effect of sampling times, sleep and food intake on the test results. Results: The median intra-individual coefficients of variations for calcium were 3.3% during night-time sleep and 2.8% during day-time sleep conditions. There was a clear diurnal variation in serum calcium, with a trough at 08.00 h in the morning after night-time sleep and a difference of approximately 0.07 mmol/L between trough and peak. Calcium was lower around the end of the sleep periods, for both night-time and day-time sleep. Food intake did not affect calcium concentrations. Conclusions: Evaluation of serum calcium results should take diurnal variation into account and allow slightly higher calcium values in the afternoon in comparison with samples collected in the morning.
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| 23. |
- Sundelin, Tina, et al.
(författare)
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Cues of fatigue : effects of sleep deprivation on facial appearance
- 2013
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Ingår i: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 36:9, s. 1355-1360
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVE: To investigate the facial cues by which one recognizes that someone is sleep deprived versus not sleep deprived.DESIGN: Experimental laboratory study.SETTING: Karolinska Institutet, Stockholm, Sweden.PARTICIPANTS: Forty observers (20 women, mean age 25 ± 5 y) rated 20 facial photographs with respect to fatigue, 10 facial cues, and sadness. The stimulus material consisted of 10 individuals (five women) photographed at 14:30 after normal sleep and after 31 h of sleep deprivation following a night with 5 h of sleep.MEASUREMENTS: Ratings of fatigue, fatigue-related cues, and sadness in facial photographs.RESULTS: The faces of sleep deprived individuals were perceived as having more hanging eyelids, redder eyes, more swollen eyes, darker circles under the eyes, paler skin, more wrinkles/fine lines, and more droopy corners of the mouth (effects ranging from b = +3 ± 1 to b = +15 ± 1 mm on 100-mm visual analog scales, P < 0.01). The ratings of fatigue were related to glazed eyes and to all the cues affected by sleep deprivation (P < 0.01). Ratings of rash/eczema or tense lips were not significantly affected by sleep deprivation, nor associated with judgements of fatigue. In addition, sleep-deprived individuals looked sadder than after normal sleep, and sadness was related to looking fatigued (P < 0.01).CONCLUSIONS: The results show that sleep deprivation affects features relating to the eyes, mouth, and skin, and that these features function as cues of sleep loss to other people. Because these facial regions are important in the communication between humans, facial cues of sleep deprivation and fatigue may carry social consequences for the sleep deprived individual in everyday life.
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| 24. |
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| 25. |
- Ziker, John, et al.
(författare)
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Indigenous peoples and demography
- 2010
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Ingår i: Anthropology News. - : American Anthropological Association. - 1541-6151 .- 1556-3502. ; 51:5, s. 10-12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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