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Aim: To study the effect of naturalistic light, programmed to replicate the spectrum distribution of natural light from dusk to dawn, on agitation measured with a Cohen-Mansfield Agitation Inventory–inspired score of nursing home residents with dementia. Background: Though the effects of different types of light on the sleep-wake patterns of senior adults and people with dementia have been examined in several studies, the effects of naturalistic light systems, as a possible nonpharmacological intervention to improve sleep and reduce agitation, have yet to be extensively evaluated due to the relative novelty of the technology. Methods: The study was designed as a 6-month pilot study of a prospective interventional longitudinal cohort study, with five participants recruited from a single department of a Danish nursing home. The effect of naturalistic lighting on agitation-associated behaviors was recorded over a 3-day period pre- and postintervention. Results: An overall 71.2% reduction in the frequency of agitation-associated behaviors was recorded, with the frequency of some behaviors even reduced by 100%. Conclusions: This pilot study estimates that naturalistic lighting may be a promising nonpharmacological intervention to improve the overall agitation of nursing home residents with dementia, with a possible added benefit of an improved work environment for the staff. This study, therefore, finds indication for the performance of a randomized controlled trial with the same intervention and a larger cohort.

Sleep-disordered breathing (SDB) occurs frequently after stroke and is associated with poor functional outcome and increased mortality. The purpose of this study was to detect changes in SDB over time after acute ischemic stroke and investigate relationships between SDB and stroke etiologies with focus on cerebral small vessel disease. From May 2015 to August 2016, we conducted an observational study of 99 patients with mild to moderate stroke (median age: 68 years, range 36–88; 56% men). Polysomnography was performed within 7 days of stroke onset (n = 91) and after 6 months (n = 52). The strokes were classified using the etiological TOAST classification. Total small vessel disease (SVD) scores were calculated based on MRIs. SDB, defined as an apnea–hypopnea index (AHI) ≥ 15, was found in 56% of patients in the acute state and in 44% at follow-up. AHI decreased over time (median change 4.7, 95% confidence interval [95% CI] 0.5–8.9; p = 0.03). Patients with AHI ≥ 15 in both the acute state and at follow-up had higher SVD score at follow-up (p = 0.003). AHI was not associated with ischemic stroke subgroups according to the TOAST classification. In conclusion, 6 months after stroke, AHI decreased, but 44% still had AHI ≥ 15. Persistent SDB in both the acute state and at follow-up was associated with a higher SVD score, but not to the TOAST subgroups. SDB evaluation should be offered to stroke patients, and the effect of SDB on cerebral small vessel disease needs to be further investigated using the well-defined SVD score. clinicaltrials.gov NCT02111408, April 11, 2014

Background: Previous studies have indicated the utility of the ADAM10-generated fragment of tau, Tau-A, as marker of neuronal damage. However, the sensitivity of the ELISA-based system was limited. Objectives: We utilized the extensive dynamic range of electrochemiluminescence compared to colorimetric assessment to improve the sensitivity of the Tau-A assay and investigate Tau-A levels after brain injury. Methods: We converted the Tau-A competitive ELISA to a competitive electrochemiluminescence-based immunoassay, Tau-A ECLIA, and compared the methods by measuring serum samples in a TBI (n = 40) and a stroke cohort (n = 64). Results: The Tau-A ECLIA was technically robust. Only 1% of the samples was below the detection limit in the ECLIA compared to 10.6% in the ELISA . Tau-A measured in both assays could discriminate between patients with a TBI and non-trauma controls (ELISA: p = 0.0005, ECLIA: p = 0.0002). The increased dynamic range of the Tau-A ECLIA also allowed discrimination between healthy controls from patients with hemorrhagic (p = 0.0172) and severe ischemic stroke (p = 0.0118) respectively, as well as patients with mild ischemic stroke from severe (p = 0.0445). Conclusions: The Tau-A ECLIA was characterized by dynamic range compared to the ELISA, which facilitated a better separation between the patient groups. Tau-A warrants further investigation as a neuronal injury associated marker.

Light therapy and the effects on biological function have been known and investigated for decades. Light therapy is used to compensate for the lack of exposure to sunlight, which is thought to be linked to major depressive disorder with seasonal patterns. It is applied as sessions with bright light mimicking natural sunlight. Lack of bright light during daytime is not the only factor to maintain the circadian rhythm, also lack of exposure to bright light at night is important. A new modality called naturalistic light shows promise, mimicking daylight by dynamically changing intensity and wavelengths throughout the day. Evidence of clinical effects, besides bright light effects on depression, is still limited, especially in hospital populations, and present review aims to extract results of the effect of any optical light intervention on hospitalized patients. Through database search, 29 trials were included, of which 8 trials used a variation of naturalistic light. Trials were heterogeneous regarding designs, populations, interventions, methods and outcomes. In 14 out of 17 studies investigating sleep duration, quality and circadian alignment, along with decreased fatigue and improved mood in daytime, light therapy had a significant effect. Circadian rhythm and rhythmicity were affected as well. The effect on mood and cognition was inconsistent across studies. Trials showed more significant outcomes when conducted in non-intensive care units and with duration5 days. Lux was reported in and compared across 24 studies and did not appear to be correlated to outcome, rather the distribution of wavelengths should be considered when conducting trials in the future. Of the 8 trials investigating naturalistic light, 4 trials had significant outcomes and 3 had adverse outcomes compared to one in the standard light regime. The overall effect of light therapy is beneficial, but evidence for the effect of naturalistic light is still insufficient to be recommended before other modalities. Future research in this area should be conducted in facilities where naturalistic light is installed, with a focus on the spectral distribution.

There exists a marked circadian variation for several bone markers (BM), which is influenced by endogenous as well as exogenous factors including hormones, physical activity, and fasting. Consequently, was the aim of this review to provide an overview of the knowledge of the circadian variation of BM and which factors influence this rhythmicity. A systematic search of PubMed was performed for studies evaluating the circadian variation of BM and which factors influence this rhythmicity. The studies were screened for eligibility by a set of predetermined criteria including a list of relevant BM and a minimum study duration of 24 h with at least 3 blood samples of which two should be at least 6 h apart. In total were 29 papers included. There exists a marked circadian variation for most BM including Carboxy-terminal Cross-Linked Telopeptide of Type I Collagen (CTX) and osteocalcin (OC) with nighttime or early morning peak. Pro-collagen Type I N-terminal Propeptide (PINP) and PTH also showed circadian rhythm but with less amplitude. The inter-osteoblast-osteoclast regulatory markers such as OPG, RANKL, FGF23, and sclerostin showed no circadian rhythm. The markers were differently affected by exogenous factors like fasting, which greatly reduced the circadian variation of CTX but did not affect PINP or OC. The marked circadian variation and the factors which influence the rhythmicity, e.g., fasting are of great consequence when measuring BM. To reduce variation and heighten validity should circadian variation and fasting be kept in mind when measuring BM.

Healthcare workers doing night shifts are at risk of lack of sleep or/and circadian rhythm disturbances. The ability to make complex rational decisions is reduced with sleep deprivation; thus, one should try to take the proper precautions. This can be done by reducing the complexity and decision speed as much as possible at nights. Furthermore, as suggested in this review, several individual and organisational measures can reduce the risk of circadian rhythm disorders and make the body ready for a new shift more quickly. Driving motor vehicles should be avoided after night shifts with insufficient sleep.

Background: Stroke patients admitted for rehabilitation often lack sufficient daytime blue light exposure due to the absence of natural light and are often exposed to light at unnatural time points. We hypothesized that artificial light imitating daylight, termed naturalistic light, would stabilize the circadian rhythm of plasma melatonin and serum cortisol levels among long-term hospitalized stroke patients. Methods: A quasi-randomized controlled trial. Stroke patients in need of rehabilitation were randomized between May 1, 2014, and June 1, 2015 to either a rehabilitation unit equipped entirely with always on naturalistic lighting (IU), or to a rehabilitation unit with standard indoor lighting (CU). At both inclusion and discharge after a hospital stay of at least 2 weeks, plasma melatonin and serum cortisol levels were measured every 4 hours over a 24-hour period. Circadian rhythm was estimated using cosinor analysis, and variance between time-points. Results: A total of 43 were able to participate in the blood collection. Normal diurnal rhythm of melatonin was disrupted at both inclusion and discharge. In the IU group, melatonin plasma levels were increased at discharge compared to inclusion (n = 23; median diff, 2.9; IQR: -1.0 to 9.9, p = 0.030) and rhythmicity evolved (n = 23; p = 0.007). In the CU group, melatonin plasma levels were similar between discharge and inclusion and no rhythmicity evolved. Overall, both patient groups showed normal cortisol diurnal rhythms at both inclusion and discharge. Conclusions: This study is the first to demonstrate elevated melatonin plasma levels and evolved rhythmicity due to stimulation with naturalistic light.

Stroke is a major cause of acquired cerebral disability among adults, frequently accompanied by depression, anxiety, cognitive impairment, disrupted sleep and fatigue. New ways of intervention to prevent these complications are therefore needed. The major circadian regulator, the suprachiasmatic nucleus, is mainly controlled by natural daylight, and the blue spectrum is considered the most powerful. During stroke rehabilitation, patients typically are mostly indoors and therefore not exposed to the natural daytime variation in light intensity. Furthermore, several rehabilitation hospitals may be exposed to powerful light in the blue spectrum, but at a time that is adversely related to their endogenous circadian phase, for example in the late evening instead of the daytime.Naturalistic light that mimics the natural daytime spectrum variation will have a positive impact on the health of poststroke patients admitted to rehabilitation. We test specifically for improved sleep and less fatigue (questionnaires, polysomnography, Actiwatch), improved well-being (questionnaires), lessen anxiety and depression (questionnaires), improved cognition (tests), stabilizing of the autonomous nervous system (ECG/HR, blood pressure, temperature) and stabilizing of the diurnal biochemistry (blood markers).The study is a prospective parallel longitudinal randomized controlled study (quasi randomization). Stroke patients in need of rehabilitation will be included at the acute stroke unit and randomized to either the intervention unit (naturalistic lighting) or the control unit (CU) (standard lighting). The naturalistic light is installed in the entire IU (Cromaviso, Denmark).This study aims to elucidate the influence of naturalistic light on patients during long-term hospitalization in a real hospital setting. The hypotheses are based on preclinical research, as studies using naturalistic light have never been performed before. Investigating the effects of naturalistic light in a clinical setting is therefore much needed.

Background Daylight entrains the central circadian pacemaker to the 24-hour day and is crucial for optimal alertness and sleep-quality. Rehabilitation patients tend to lack exposure to sufficient natural light. Objective Installed diurnal naturalistic light may reduce the known disrupted sleep quality and fatigue seen in post stroke patients. Methods Stroke patients were randomized to either an intervention rehabilitation unit (IU) equipped with naturalistic lighting (artificial sunlight spectrum) or to a control rehabilitation unit (CU) with standard indoor lighting. At inclusion and discharge, fatigue and subjective sleep quality were measured. Results Ninety stroke patients were included between May 2014, and June 2015. At discharge, patients from the IU experienced less fatigue than the CU patients, based on the Multidimensional Fatigue Inventory questionnaire general (IU, n = 28; CU, n = 30; diff - 20.6%, 95% confidence interval (CI) [- 35.0%; - 3.0%]; P = 0.025) and the Rested Statement (IU, n = 28; CU, n = 30; diff + 41.6%, 95% CI [+4.6%; +91.8%]; P = 0.025). No differences were detected between groups in sleepiness or subjective sleep quality by the Pittsburgh Sleep Quality Index. Conclusions Fatigue was significantly reduced in rehabilitation patients exposed to naturalistic lighting during admission.

Background Patients admitted for rehabilitation often lack sufficient natural light to entrain their circadian rhythm. Objective Installed diurnal naturalistic light may positively influence the outcome of depressive mood, anxiety, and cognition in such patients. Methods A quasi-randomized controlled trial. Ninety stroke patients in need of rehabilitation were randomized between May 1, 2014, and June 1, 2015 to either a rehabilitation unit equipped entirely with always on naturalistic lighting (IU), or to a rehabilitation unit with standard indoor lighting (CU).Examinations were performed at inclusion and discharge. The following changes were investigated: depressive mood based on the Hamilton Depression scale (HAM-D6) and Major Depression Inventory scale (MDI), anxiety based on the Hospital Anxiety and Depression Scale (HADS), cognition based on the Montreal Cognitive Assessment (MoCA) and well-being based on the Well-being Index (WHO-5). Results Depressive mood (MDI p = 0.0005, HAM-D6 p = 0.011) and anxiety (HADS anxiety p = 0.045) was reduced, and well-being (WHO-5 p = 0.046) was increased, in the IU at discharge compared to the CU. No difference was found in cognition (MoCA p = 0.969). Conclusions This study is the first to demonstrate that exposure to naturalistic light during admission may significantly improve mental health in rehabilitation patients. Further studies are needed to confirm these findings.

Introduction: Stroke is a major cause of acquired cerebral disability among adults, frequently accompanied by depression. New ways of intervention to prevent post stroke depression is therefore needed. The blue light spectrum is the strongest zeitgeber (time-giver) and is known to stabilize the circadian rhythm. Patients admitted for rehabilitation are often lacking the blue light in daytime due to the long indoor admission; furthermore, they are often exposed to blue light in the evenings, as blue light is contained in standard lightning. Hypothesis: Circadian light will reduce depressive mood in stroke patients admitted for rehabilitation. Methods: The study is a prospective parallel longitudinal randomized controlled study (quasi randomization). Stroke patients in need of rehabilitation were included at the acute stroke unit and randomized to either the intervention unit (IU)(circadian lighting) or the control unit (CU)(standard lighting). The circadian light was installed in the entire IU (Cromaviso, Denmark). Examination was done in the acute unit and at discharge after at least 2 weeks in the IU/CU. Change in depressive mood was measured by the Hamilton Rating Scale for Depression (HAM-D 6 ) and The Major Depression Inventory scale (MDI). Results: Patients were included over a year (N=90), 6 did not reach randomization, 45 were randomized to the IU, and 39 to the CU. A sample of 59 and 62 patients were able to answer the HAM-D 6 (N=30IU;N=29CU) and MDI (N=30IU;N=29CU) score, respectively. Both scores were significantly lower in the intervention group at discharged compared with the control group (ANCOVA, antidepressants medicine was included as a confounder, HAM-D 6 , P=0.018, Estimate=-2.25;SEM=0.92, MDI, P=0.009, Estimate=-4.72;SEM=1.74). Conclusion: Our findings show for the first time circadian light as a beneficial intervention on depressive mood on long-term hospitalized patients in a real hospital setting. The circadian lightning should be considered as an integrated segment in the environment of rehabilitation units.

Several studies have indicated that the population in general perceives doctors as reliable. In the present study perceptions of reliability and kindness attributed to another socially significant archetype, Santa Claus, have been comparatively examined in relation to the doctor.In all, 52 randomly chosen participants were shown a film, where a narrator dressed either as Santa Claus or as a doctor tells an identical story. Structured interviews were then used to assess the subjects' perceptions of reliability and kindness in relation to the narrator's appearance.We found a strong inclination for Santa Claus being perceived as friendlier than the doctor (p = 0.053). However, there was no significant difference in the perception of reliability between Santa Claus and the doctor (p = 0.524).The positive associations attributed to Santa Claus probably cause that he is perceived friendlier than the doctor who may be associated with more serious and unpleasant memories of illness and suffering. Surprisingly, and despite him being an imaginary person, Santa Claus was assessed as being as reliable as the doctor.

Aims Elevated non-fasting triglycerides mark elevated levels of remnant cholesterol. Using a Mendelian randomization approach, we tested whether genetically increased remnant cholesterol in hypertriglyceridaemia due to genetic variation in the apolipoprotein A5 gene ( APOA5 ) associates with an increased risk of myocardial infarction (MI). Methods and results We resequenced the core promoter and coding regions of APOA5 in individuals with the lowest 1% ( n = 95) and highest 2% ( n = 190) triglyceride levels in the Copenhagen City Heart Study (CCHS, n = 10 391). Genetic variants which differed in frequency between the two extreme triglyceride groups (c.-1131T > C, S19W, and c.*31C > T; P -value: 0.06 to