206 research outputs found
The evaluation of melatonin as a possible antidepressive
Get PDFMelatonin, a hormone of the pineal gland, was evaluated in a variety of animal models of depression. Measurements of the frog righting reflex and rat locomotor activity showed that low doses of melatonin have a serotonin-like potentiating effect following monoamine oxidase inhibition. High doses of melatonin caused a reduction in the duration of rat immobility in the Porsolt model of depression and exerted a chlorpromazine-like effect on conditioned avoidance behaviour. In view of the indoleamine hypothesis of depressive disorders, the possibility of melatonin being a potential antidepressive is discussed and it is concluded that melatonin might be useful in the treatment of "agitated" depression
Visual impairment and circadiam rhythm disorders
Get PDFMany aspects of human physiology and behavior are dominated by 24-hour circadian rhythms that have a major impact on our health and well-being, including the sleep-wake cycle, alertness and performance patterns, and many daily hormone profiles. These rhythms are spontaneously generated by an internal âpacemakerâ in the hypothalamus, and daily light exposure to the eyes is required to keep these circadian rhythms synchronized both internally and with the external environment Sighted individuals take this daily synchronization process for granted, although they experience some of the consequences of circadian desynchrony when âjetlaggedâ or working night shifts. Most blind people with no perception of light, however, experience continual circadian desynchrony through a failure of light information to reach the hypothalamic circadian clock, resulting in cyclical episodes of poor sleep and daytime dysfunction. Daily melatonin administration, which provides a replacement synchronizing daily âtime cue,â is a promising therapeutic strategy, although optimal treatment dose and timing remain to be determined
Resetting the late timing of ânight owlsâ has a positive impact on mental health and performance
Get PDFBackground
There is conflict between living according to our endogenous biological rhythms and our
external environment, with disruptions resulting in negative consequences to health and performance.
This is often documented in shift work and jet lag, but âsocietal normsâ (eg, typical working hours) can
create profound issues for ânight owlsâ, people whose internal biological timing predisposes them to
follow an unusually late sleep-wake cycle. Night owls have also been associated with health issues, mood
disturbances, poorer performance and increased mortality rates.
Methods
This study used a randomized control trial design aimed to shift the late timing of night owls to
an earlier time (phase advance), using non-pharmacological, practical interventions in a real-world
setting. These interventions targeted light exposure (through earlier wake up/sleep times), fixed meals
times, caffeine intake and exercise.
Results
Overall, participants demonstrated a significant advance of ~2 h in sleep/wake timings as
measured by actigraphy and circadian phase markers (dim light melatonin onset and peak time of the
cortisol awakening response), whilst having no adverse effect on sleep duration. Notably, the phase
advance was accompanied by significant improvements to self-reported depression and stress, as well as
improved cognitive (reaction time) and physical (grip strength) performance measures during the typical
'suboptimal morning hours.
Conclusions
Our findings propose a novel strategy for shifting clock timing towards a pattern that is
more aligned to societal demands that could significantly improve elements of performance, mental
health and sleep timing in the real world.</p
Evaluation of mRNA markers for estimating blood deposition time : towards alibi testing from human forensic stains with rhythmic biomarkers
Get PDFThis study was supported by grant 27.011.001 by the Netherlands Organization for Scientific Research (NWO) Forensic Science Program, Erasmus MC University Medical Center Rotterdam, by the EU 6th Framework project EUCLOCK (018741), UK Biotechnology and Biological Sciences Research Council (BBSRC) Grant BB/I019405/1, and by a previous grant from the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) within the framework of the Forensic Genomics Consortium Netherlands (FGCN). D.J.S. is a Royal Society Wolfson Research Merit Award holder.Determining the time a biological trace was left at a scene of crime reflects a crucial aspect of forensic investigations as - if possible - it would permit testing the sample donor's alibi directly from the trace evidence, helping to link (or not) the DNA-identified sample donor with the crime event. However, reliable and robust methodology is lacking thus far. In this study, we assessed the suitability of mRNA for the purpose of estimating blood deposition time, and its added value relative to melatonin and cortisol, two circadian hormones we previously introduced for this purpose. By analysing 21 candidate mRNA markers in blood samples from 12 individuals collected around the clock at 2 h intervals for 36 h under real-life, controlled conditions, we identified 11 mRNAs with statistically significant expression rhythms. We then used these 11 significantly rhythmic mRNA markers, with and without melatonin and cortisol also analysed in these samples, to establish statistical models for predicting day/night time categories. We found that although in general mRNA-based estimation of time categories was less accurate than hormone-based estimation, the use of three mRNA markers HSPA1B, MKNK2 and PER3 together with melatonin and cortisol generally enhanced the time prediction accuracy relative to the use of the two hormones alone. Our data best support a model that by using these five molecular biomarkers estimates three time categories, i.e., night/early morning, morning/noon, and afternoon/evening with prediction accuracies expressed as AUC values of 0.88, 0.88, and 0.95, respectively. For the first time, we demonstrate the value of mRNA for blood deposition timing and introduce a statistical model for estimating day/night time categories based on molecular biomarkers, which shall be further validated with additional samples in the future. Moreover, our work provides new leads for molecular approaches on time of death estimation using the significantly rhythmic mRNA markers established here.PostprintPeer reviewe
Improving fatigue risk management in healthcare: A systematic scoping review of sleep-related/fatigue-management interventions for nurses and midwives.
Get PDFBackground. Nurses and midwives make up almost 50% of the global healthcare shift working workforce. Shift work interferes with sleep and causes fatigue with adverse effects for nursesâ and midwivesâ health, as well as on patient safety and care. Where other safety-critical sectors have developed Fatigue Risk Management Systems, healthcare is behind the curve; with published literature only focussing on the evaluation of discreet sleep-related/fatigue-management interventions. Little is known, however, about which interventions have been evaluated for nurses and midwives. Our review is a critical first step to building the evidence-base for healthcare organisations seeking to address this important operational issue.
Objectives. We address two questions: 1) What sleep-related/fatigue-management interventions have been assessed in nurses and midwives and what is their evidence-base? and 2) What measures are used by researchers to assess intervention effectiveness?
Design & data sources. The following databases were searched in November, 2018 with no limit on publication dates: MEDLINE, PsychINFO and CINAHL.
Review methods. We included: 1. studies conducted in adult samples of nurses and/or midwives that had evaluated a sleep-related/fatigue-management intervention; and 2. studies that reported intervention effects on fatigue, sleep, or performance at work, and on measures of attention or cognitive performance (as they relate to the impact of shift working on patient safety/care).
Results. The search identified 798 potentially relevant articles, out of which 32 met our inclusion criteria. There were 8619 participants across the included studies and all were nurses (88.6% female). We did not find any studies conducted in midwives nor any studies conducted in the UK, with most studies conducted in the US, Italy and Taiwan. There was heterogeneity both in terms of the interventions evaluated and the measures used to assess effectiveness. Napping could be beneficial but there was wide variation regarding nap duration and timing, and we need to understand more about barriers to implementation. Longer shifts, shift patterns including nights, and inadequate recovery time between shifts (quick returns) were associated with poorer sleep, increased sleepiness and increased levels of fatigue. Light exposure and/or light attenuation interventions showed promise but the literature was dominated by small, potentially unrepresentative samples.
Conclusions. The literature related to sleep-related/fatigue-management interventions for nurses and midwives is fragmented and lacks cohesion. Further empirical work is warranted with a view to developing comprehensive Fatigue Risk Management Systems to protect against fatigue in nurses, midwives, and other shift working healthcare staff
THE INFLUENCE OF THE VARIOUS TEMPERATURES ON THE PUPAS OF MEDITERRANEAN FRUITFLY AND ON THE EARLY DEVELOPMENT OF PLASE OPIUS CONCOLORA SZEPL
Get PDFThe identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study. Statistically significant rhythms in expression were observed for STAT3, SREBF1, TRIB1, and THRA1 in samples from both the S/SD and the CR studies, indicating that their rhythmicity is driven by the endogenous clock. The MKNK2 gene was significantly rhythmic in the S/SD but not the CR study, which implies its exogenously driven rhythmic expression. In addition, we confirmed the circadian expression of PER1, PER3, and REV-ERBα in the CR study samples, while BMAL1 and HSPA1B were not significantly rhythmic in the CR samples; all 5 genes previously showed significant expression in the S/SD study samples. Overall, our results demonstrate that rhythmic expression patterns of clock and selected clock-controlled genes in human blood cells are in part determined by exogenous factors (sleep and fasting state) and in part by the endogenous circadian timing system. Knowledge of the exogenous and endogenous regulation of gene expression rhythms is needed prior to the selection of potential candidate marker genes for future applications in medical and forensic settings
Blue-enriched white light improves performance but not subjective alertness and circadian adaptation during three consecutive simulated night shifts
Get PDFUse of blue-enriched light has received increasing interest regarding its activating and performance sustaining effects. However, studies assessing effects of such light during night work are few, and novel strategies for lighting using light emitting diode (LED) technology need to be researched. In a counterbalanced crossover design, we investigated the effects of a standard polychromatic blue-enriched white light (7000 K; âŒ200 lx) compared to a warm white light (2500 K), of similar photon density (âŒ1.6 Ă 1014 photons/cm2/s), during three consecutive simulated night shifts. A total of 30 healthy participants [10 males, mean age 23.3 (SD = 2.9) years] were included in the study. Dependent variables comprised subjective alertness using the Karolinska Sleepiness Scale, a psychomotor vigilance task (PVT) and a digit symbol substitution test (DSST), all administered at five time points throughout each night shift. We also assessed dim-light melatonin onset (DLMO) before and after the night shifts, as well as participantsâ opinion of the light conditions. Subjective alertness and performance on the PVT and DSST deteriorated during the night shifts, but 7000 K light was more beneficial for performance, mainly in terms of fewer errors on the PVT, at the end of the first- and second- night shift, compared to 2500 K light. Blue-enriched light only had a minor impact on PVT response times (RTs), as only the fastest 10% of the RTs were significantly improved in 7000 K compared to 2500 K light. In both 7000 and 2500 K light, the DLMO was delayed in those participants with valid assessment of this parameter [n = 20 (69.0%) in 7000 K light, n = 22 (78.6%) in 2500 K light], with a mean of 2:34 (SE = 0:14) and 2:12 (SE = 0:14) hours, respectively, which was not significantly different between the light conditions. Both light conditions were positively rated, although participants found 7000 K to be more suitable for work yet evaluated 2500 K light as more pleasant. The data indicate minor, but beneficial, effects of 7000 K light compared to 2500 K light on performance during night work. Circadian adaptation did not differ significantly between light conditions, though caution should be taken when interpreting these findings due to missing data. Field studies are needed to investigate similar light interventions in real-life settings, to develop recommendations regarding illumination for night workers.publishedVersio
Synchrony between daily rhythms of malaria parasites and hosts is driven by an essential amino acid
Get PDFBackground: Rapid asexual replication of blood stage malaria parasites is responsible for the severity of disease symptoms and fuels the production of transmission forms. Here, we demonstrate that a Plasmodium chabaudi's schedule for asexual replication can be orchestrated by isoleucine, a metabolite provided to the parasite in a periodic manner due to the host's rhythmic intake of food. Methods: We infect female C57BL/6 and Per1/2-null mice which have a disrupted canonical (transcription translation feedback loop, TTFL) clock with 1Ă10 5 red blood cells containing P. chabaudi (DK genotype). We perturb the timing of rhythms in asexual replication and host feeding-fasting cycles to identify nutrients with rhythms that match all combinations of host and parasite rhythms. We then test whether perturbing the availability of the best candidate nutrient in vitro changes the schedule for asexual development. Results: Our large-scale metabolomics experiment and follow up experiments reveal that only one metabolite - the amino acid isoleucine - fits criteria for a time-of-day cue used by parasites to set the schedule for replication. The response to isoleucine is a parasite strategy rather than solely the consequences of a constraint imposed by host rhythms, because unlike when parasites are deprived of other essential nutrients, they suffer no apparent costs from isoleucine withdrawal. Conclusions: Overall, our data suggest parasites can use the daily rhythmicity of blood-isoleucine concentration to synchronise asexual development with the availability of isoleucine, and potentially other resources, that arrive in the blood in a periodic manner due to the host's daily feeding-fasting cycle. Identifying both how and why parasites keep time opens avenues for interventions; interfering with the parasite's time-keeping mechanism may stall replication, increasing the efficacy of drugs and immune responses, and could also prevent parasites from entering dormancy to tolerate drugs
Investigation of metabolites for estimating blood deposition time
Get PDFThis study was supported by a UK Biotechnology and Biological Sciences Research Council (BBSRC) Grant (BB/I019405/1) to DJS, grant 727.011.001 from the Netherlands Organization for Scientific Research (NWO) Forensic Science Program to MK and by Erasmus MC University Medical Centre Rotterdam. DJS is a Royal Society Wolfson Research Merit Award holder. RAH and IH were funded by the Dutch applied research foundation (STW Perspectief Program âOnTimeâ project 12185).Trace deposition timing reflects a novel concept in forensic molecular biology involving the use of rhythmic biomarkers for estimating the time within a 24-h day/night cycle a human biological sample was left at the crime scene, which in principle allows verifying a sample donorâs alibi. Previously, we introduced two circadian hormones for trace deposition timing and recently demonstrated that messenger RNA (mRNA) biomarkers significantly improve time prediction accuracy. Here, we investigate the suitability of metabolites measured using a targeted metabolomics approach, for trace deposition timing. Analysis of 171 plasma metabolites collected around the clock at 2-h intervals for 36 h from 12 male participants under controlled laboratory conditions identified 56 metabolites showing statistically significant oscillations, with peak times falling into three day/night time categories: morning/noon, afternoon/evening and night/early morning. Time prediction modelling identified 10 independently contributing metabolite biomarkers, which together achieved prediction accuracies expressed as AUC of 0.81, 0.86 and 0.90 for these three time categories respectively. Combining metabolites with previously established hormone and mRNA biomarkers in time prediction modelling resulted in an improved prediction accuracy reaching AUCs of 0.85, 0.89 and 0.96 respectively. The additional impact of metabolite biomarkers, however, was rather minor as the previously established model with melatonin, cortisol and three mRNA biomarkers achieved AUC values of 0.88, 0.88 and 0.95 for the same three time categories respectively. Nevertheless, the selected metabolites could become practically useful in scenarios where RNA marker information is unavailable such as due to RNA degradation. This is the first metabolomics study investigating circulating metabolites for trace deposition timing, and more work is needed to fully establish their usefulness for this forensic purpose.Publisher PDFPeer reviewe
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