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- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 4. |
- Aho, Vilma, et al.
(författare)
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Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways : Experimental and Epidemiological Studies in Humans
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-kappa B signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases.
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| 7. |
- van Leeuwen, Wessel M A, et al.
(författare)
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Sleep, Sleepiness, and Neurobehavioral Performance While on Watch in a Simulated 4 Hours on/8 Hours off Maritime Watch System
- 2013
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Ingår i: Annual Review of Chronopharmacology. - : Informa UK Limited. - 0743-9539 .- 1525-6073 .- 0742-0528. ; 30:9, s. 1108-1115
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Tidskriftsartikel (refereegranskat)abstract
- Seafarer sleepiness jeopardizes safety at sea and has been documented as a direct or contributing factor in many maritime accidents. This study investigates sleep, sleepiness, and neurobehavioral performance in a simulated 4 h on/8 h off watch system as well as the effects of a single free watch disturbance, simulating a condition of overtime work, resulting in 16 h of work in a row and a missed sleep opportunity. Thirty bridge officers (age 30 +/- 6 yrs; 29 men) participated in bridge simulator trials on an identical 1-wk voyage in the North Sea and English Channel. The three watch teams started respectively with the 00-04, the 04-08, and the 08-12 watches. Participants rated their sleepiness every hour (Karolinska Sleepiness Scale [KSS]) and carried out a 5-min psychomotor vigilance test (PVT) test at the start and end of every watch. Polysomnography (PSG) was recorded during 6 watches in the first and the second half of the week. KSS was higher during the first (mean +/- SD: 4.0 +/- 0.2) compared with the second (3.3 +/- 0.2) watch of the day (p
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| 8. |
- Abrahamsen, Annbjørg Selma, et al.
(författare)
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Impact of work exposure on cognitive performance in Faroese deep-sea fishers : a field study
- 2022
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Ingår i: International Maritime Health. - 1641-9251 .- 2081-3252. ; 73:3, s. 150-161
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study examines the impact of work-related exposure on the cognitive performance of Faroese deep-sea fishers. Faroese fishing crews work long hours in demanding and noisy environments amidst highly uncertain and challenging weather conditions. These factors, together with compromised patterns of rest and sleep, are known to increase fatigue. Our aim was to study if changes could be measured in fishers’ cognitive performance at the end of the trip when compared with the baseline measure at the beginning.Materials and methods: Data was collected over 15 months (May 2017 to July 2018) from 157 fishers on 18 fishing trips which involved 202 investigative days on board. Questionnaires and six computerised cognitive tests: Simple Reaction Time, Numeric Working Memory, Corsi Blocks, Rapid Visual Information Processing, Digit Vigilance, and Card Sorting Test were used for data collection at the beginning and end of the trip. Differences between the outcomes on the two test points were analysed with one-way ANOVA comparing the performances at the beginning and end of the voyage, and two-way ANOVA to examine the interactive effect of chronotype and test occasions on the outcomes. Mixed models were used to test for the effects of predictor variables.Results: Significant declines in cognitive performance were observed from the beginning to the end of the trip, with decreases in visuospatial memory and reaction times, and increases in cognitive lapses. Furthermore, slowing in response times was observed in the second half of the Digit Vigilance test when comparing the halves.Conclusions: Declines in performance were observed from the start to the end of the trip. Furthermore, fishers performed significantly worse in the second half of some parted tests, and evening types seem less influenced by irregular work hours. These findings call for improving the safety of the vessels and their crew.
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| 9. |
- Abrahamsen, Annbjørg Selma, et al.
(författare)
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Working environment and fatigue among fishers in the north Atlantic : a field study
- 2023
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Ingår i: International Maritime Health. - 1641-9251 .- 2081-3252. ; 74:1, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study investigates how Faroese deep-sea fishers’ exposure to work-related stressors affects their sleep, sleepiness, and levels of fatigue. Being constantly exposed to the unpredictable and harsh North Atlantic Ocean, having long work hours and split sleep for up to 40 days consecutively, they will arguably suffer from fatigue.Materials and methods: One hundred and fifty seven fishers participated in this study, and data was gathered throughout 202 days at sea. Subjective data was collected at the start and end of trips via questionnaires, sleep and sleepiness diaries and supplemented by objective sleep data through actigraphs. Ship movements were logged with a gyroscope connected to a laptop. A noise metre measured each work station and resting area, and noise exposure profiles were calculated based on each participant’s activity and location. Linear mixed-effect models investigated the effects of work exposure variables on sleep efficiency, and cumulative link mixed models measured effects on the Karolinska Sleepiness Scale and physical fatigue scale.Results: Time of day followed by ship movement were the exposure variables with the highest impact on the outcome variables of sleep efficiency, sleepiness and physical fatigue. The number of days at sea revealed correlations to outcome variables either by itself or interacting with the sleep periods per day. Crew size, shift system or noise did not impact outcome variables when in the model with other variables. Larger catches improved sleep efficiency but did not affect sleepiness and physical fatigue ratings.Conclusions: The findings indicate a chronically fatigued fisher population, and recommends urgent attention being paid to improving the structure of vessels and installing stabilators for greater stability at sea; work schedules being evaluated for protection of health; and work environments being designed that fulfill human physiological requirements in order to ensure the wellbeing and safety of those at sea.
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