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Mitotic errors lead to aneuploidy, a condition of karyotype imbalance, frequently found in cancer cells. Alterations in chromosome copy number induce a wide variety of cellular stresses, including genome instability. Here, we show that cancer cells might exploit aneuploidy-induced genome instability and the resulting gene copy-number changes to survive under conditions of selective pressure, such as chemotherapy. Resistance to chemotherapeutic drugs was dictated by the acquisition of recurrent karyotypes, indicating that gene dosage might play a role in driving chemoresistance. Thus, our study establishes a causal link between aneuploidy-driven changes in gene copy number and chemoresistance and might explain why some chemotherapies fail to succeed.

IntroductionInternational guidelines include early nutritional support (≤48 hour after admission), 20–25 kcal/kg/day, and 1.2–2 g/kg/day protein at the acute phase of critical illness. Recent data challenge the appropriateness of providing standard amounts of calories and protein during acute critical illness. Restricting calorie and protein intakes seemed beneficial, suggesting a role for metabolic pathways such as autophagy, a potential key mechanism in safeguarding cellular integrity, notably in the muscle, during critical illness. However, the optimal calorie and protein supply at the acute phase of severe critical illness remains unknown. NUTRIREA-3 will be the first trial to compare standard calorie and protein feeding complying with guidelines to low-calorie low-protein feeding. We hypothesised that nutritional support with calorie and protein restriction during acute critical illness decreased day 90 mortality and/or dependency on intensive care unit (ICU) management in mechanically ventilated patients receiving vasoactive amine therapy for shock, compared with standard calorie and protein targets.Methods and analysisNUTRIREA-3 is a randomised, controlled, multicentre, open-label trial comparing two parallel groups of patients receiving invasive mechanical ventilation and vasoactive amine therapy for shock and given early nutritional support according to one of two strategies: early calorie-protein restriction (6 kcal/kg/day-0.2–0.4 g/kg/day) or standard calorie-protein targets (25 kcal/kg/day, 1.0–1.3 g/kg/day) at the acute phase defined as the first 7 days in the ICU. We will include 3044 patients in 61 French ICUs. Two primary end-points will be evaluated: day 90 mortality and time to ICU discharge readiness. The trial will be considered positive if significant between-group differences are found for one or both alternative primary endpoints. Secondary outcomes include hospital-acquired infections and nutritional, clinical and functional outcomes.Ethics and disseminationThe NUTRIREA-3 study has been approved by the appropriate ethics committee. Patients are included after informed consent. Results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT03573739.

Introduction Most adults with moderate to severe traumatic brain injury (TBI) report persistent sleep-wake disturbances. Whether these complaints are either associated with abnormal sleep-wake patterns or can be explained by TBI-related characteristics is unclear. The present study aimed at characterising the subjective and objective sleep-wake patterns in TBI adults by taking into consideration the influence of TBI severity, common comorbidities and psychoactive medication. Methods Overall, 34 adults with moderate-severe TBI (one to four years post-injury) were compared to 34 controls. Sleepiness, fatigue, sleep quality, mood, and pain were assessed with questionnaires. A seven day sleep diary and actigraphy was used to document sleep and wake patterns. Results Compared to controls, TBI participants reported more sleepiness and fatigue, as well as poorer sleep quality. On actigraphy, they had earlier bedtime and longer time spent in bed, but equivalent sleep efficiency during the nighttime episode compared to controls. TBI participants also took more naps and accumulated more time asleep over the 24 h period than controls. These group differences were accentuated when only TBI adults using psychoactive medication were included. More comorbidities, more severe injuries and longer hospital stay were positively correlated with fatigue, sleepiness and sleep duration. Conclusions Our results showed that despite complaints regarding sleep and diurnal functioning, TBI survivors have very marginal changes in their objective sleep-wake schedules. Prolonged time spent in bed may reflect an attempt to increase their sleep duration in response to fatigue and sleepiness. TBI adults who use psychoactive medication are those with more evident changes in their sleep-wake schedules.

Erratum inCorrection to Lancet Respir Med 2021; published online April 19. https://doi.org/10.1016/S2213-2600(21)00096-5.; International audience; Background: In the Île-de-France region (henceforth termed Greater Paris), extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) was considered early in the COVID-19 pandemic. We report ECMO network organisation and outcomes during the first wave of the pandemic.Methods: In this multicentre cohort study, we present an analysis of all adult patients with laboratory-confirmed SARS-CoV-2 infection and severe ARDS requiring ECMO who were admitted to 17 Greater Paris intensive care units between March 8 and June 3, 2020. Central regulation for ECMO indications and pooling of resources were organised for the Greater Paris intensive care units, with six mobile ECMO teams available for the region. Details of complications (including ECMO-related complications, renal replacement therapy, and pulmonary embolism), clinical outcomes, survival status at 90 days after ECMO initiation, and causes of death are reported. Multivariable analysis was used to identify pre-ECMO variables independently associated with 90-day survival after ECMO.Findings: The 302 patients included who underwent ECMO had a median age of 52 years (IQR 45-58) and Simplified Acute Physiology Score-II of 40 (31-56), and 235 (78%) of whom were men. 165 (55%) were transferred after cannulation by a mobile ECMO team. Before ECMO, 285 (94%) patients were prone positioned, median driving pressure was 18 cm H2O (14-21), and median ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen was 61 mm Hg (IQR 54-70). During ECMO, 115 (43%) of 270 patients had a major bleeding event, 27 of whom had intracranial haemorrhage; 130 (43%) of 301 patients received renal replacement therapy; and 53 (18%) of 294 had a pulmonary embolism. 138 (46%) patients were alive 90 days after ECMO. The most common causes of death were multiorgan failure (53 [18%] patients) and septic shock (47 [16%] patients). Shorter time between intubation and ECMO (odds ratio 0·91 [95% CI 0·84-0·99] per day decrease), younger age (2·89 [1·41-5·93] for ≤48 years and 2·01 [1·01-3·99] for 49-56 years vs ≥57 years), lower pre-ECMO renal component of the Sequential Organ Failure Assessment score (0·67, 0·55-0·83 per point increase), and treatment in centres managing at least 30 venovenous ECMO cases annually (2·98 [1·46-6·04]) were independently associated with improved 90-day survival. There was no significant difference in survival between patients who had mobile and on-site ECMO initiation.Interpretation: Beyond associations with similar factors to those reported on ECMO for non-COVID-19 ARDS, 90-day survival among ECMO-assisted patients with COVID-19 was strongly associated with a centre's experience in venovenous ECMO during the previous year. Early ECMO management in centres with a high venovenous ECMO case volume should be advocated, by applying centralisation and regulation of ECMO indications, which should also help to prevent a shortage of resources.

The overall structure and composition of human centromeres have been well reported, but how these elements vary between individual chromosomes and influence the chromosome-specific behavior during mitosis remains untested. In our study, we discover the existence of heterogeneity of centromeric DNA features that dictates the chromosome segregation fidelity during mitosis.

Tumour evolution is driven by both genetic and epigenetic changes. CENP-A, the centromeric histone H3 variant, is an epigenetic mark that directly perturbs genetic stability and chromatin when overexpressed. Although CENP-A overexpression is a common feature of many cancers, how this impacts cell fate and response to therapy remains unclear. Here, we established a tunable system of inducible and reversible CENP-A overexpression combined with a switch in p53 status in human cell lines. Through clonogenic survival assays, single-cell RNA-sequencing and cell trajectory analysis, we uncover the tumour suppressor p53 as a key determinant of how CENP-A impacts cell state, cell identity and therapeutic response. If p53 is functional, CENP-A overexpression promotes senescence and radiosensitivity. Surprisingly, when we inactivate p53, CENP-A overexpression instead promotes epithelial-mesenchymal transition, an essential process in mammalian development but also a precursor for tumour cell invasion and metastasis. Thus, we uncover an unanticipated function of CENP-A overexpression to promote cell fate reprogramming, with important implications for development and tumour evolution., Jeffery et al. develop a system of inducible and reversible CENP-A overexpression, combined with a switch in p53 status in human cell lines. They find the tumor suppressor p53 as a key determinant of how CENP-A impacts cell state, cell identity and therapeutic response. This study suggests that CENP-A overexpression promotes the reprogramming of cell fates in the context of tumor evolution.

Christophe Moderie,1,2 Solenne Van der Maren,1,3 Jean Paquet,1 Marie Dumont1,4 1Center for Advanced Research in Sleep Medicine, Sacre-Coeur Hospital, CIUSSS-NIM, Montreal, Quebec, Canada; 2Department of Psychiatry, McGill University, Montreal, Quebec, Canada; 3Department of Psychology, University of Montreal, Montreal, Quebec, Canada; 4Department of Psychiatry, University of Montreal, Montreal, Quebec, CanadaCorrespondence: Marie DumontCenter for Advanced Research in Sleep Medicine (J-5185), Sacre-Coeur Hospital of Montreal, CIUSSS-NIM, 5400 Boul. Gouin Ouest, Montreal, QC H4J 1C5, CanadaTel +1 514 338 2222, x-2246Fax +1 514 338 2531Email Marie.dumont@umontreal.caBackground: Individuals complaining of a delayed sleep schedule are expected to have shorter sleep duration and lower sleep quality when they must comply with morning obligations. The changes in the sleep schedule imposed by morning obligations may in turn decrease the stability and amplitude of their rest-activity cycle. These expectations were only partially supported in previous studies, possibly due to poor differentiation between days with mandatory or free wake times.Participants: Fourteen college/university students (8 women) with a complaint of a late sleep schedule and a bedtime after midnight were compared to fourteen controls with an earlier sleep schedule and no complaint.Methods: During a week of 24-h activity recording, participants specified in their sleep diary whether their wake time was free or determined by an obligation.Results: The number of nights with mandatory wake times was similar in the two groups. Groups were also similar for sleep duration and sleep quality over the 7 days of recording. Actigraphic sleep efficiency was the same in the two groups for both free and mandatory wake times, but subjective sleep quality decreased on the nights with mandatory wake time in both groups. On the nights with mandatory wake time, delayed participants had shorter sleep episodes and less total sleep time than controls. Rest-activity cycle amplitude was lower in the delayed group whether wake time was free or mandatory.Conclusion: Sleep duration and total sleep time differed between the two groups only when wake time was mandatory. Prior to mandatory wake times, delayed participants kept the same bedtime and shortened their sleep; sleep latency and sleep efficiency were preserved but subjective sleep quality and alertness on awakening decreased compared to nights with free wake time. Lower amplitude of the rest-activity cycle in delayed subjects may reflect lifestyle differences compared to control participants.Keywords: sleep schedule, circadian sleep disorders, chronotype, ambulatory recordings, delayed sleep-wake phase disorder, social jetlag

BACKGROUND Crohn's disease (CD) and hidradenitis suppurativa (HS), a chronic inflammatory skin disease, induce similar inflammatory lesions of the groin and gluteal area. Both diseases are characterised by an inadequate immune response to commensal bacteria in genetically predisposed subjects and can be associated. AIM To assess whether HS was associated with clinical and prognostic factors in CD. METHODS A retrospective case-control study included 4645 patients with CD referred to Saint-Antoine Hospital gastroenterology tertiary care centre between 2003 and 2016. Matching variables were sex, age, age and the presence of perianal lesions at CD diagnosis, follow-up quality. HS was confirmed by dermatological examination; location, phenotype and severity (Hurley staging) were recorded. RESULTS Hidradenitis suppurativa prevalence was 0.95% (44 cases); 80% of patients displayed Hurley stage II or III disease. CD preceded HS in 70% of cases with a median interval of 9 years (IQR 5.25-12.75). CD with HS was more active (56% vs 40% years with active disease, P

Intrinsic genomic features of individual chromosomes can contribute to chromosome-specific aneuploidy. Centromeres are key elements for the maintenance of chromosome segregation fidelity via a specialized chromatin marked by CENP-A wrapped by repetitive DNA. These long stretches of repetitive DNA vary in length among human chromosomes. Using CENP-A genetic inactivation in human cells, we directly interrogate if differences in the centromere length reflect the heterogeneity of centromeric DNA-dependent features and whether this, in turn, affects the genesis of chromosome-specific aneuploidy. Using three distinct approaches, we show that mis-segregation rates vary among different chromosomes under conditions that compromise centromere function. Whole-genome sequencing and centromere mapping combined with cytogenetic analysis, small molecule inhibitors, and genetic manipulation revealed that inter-chromosomal heterogeneity of centromeric features, but not centromere length, influences chromosome segregation fidelity. We conclude that faithful chromosome segregation for most of human chromosomes is biased in favor of centromeres with high abundance of DNA-dependent centromeric components. These inter-chromosomal differences in centromere features can translate into non-random aneuploidy, a hallmark of cancer and genetic diseases.

A number of factors can contribute to a delayed sleep schedule. An important factor could be a daily profile of light exposure favoring a later circadian phase. This study aimed to compare light exposure between 14 young adults complaining of a delayed sleep schedule and 14 matched controls and to identify possible associations between habitual light exposure and circadian phase. Exposure to white and blue light was recorded with ambulatory monitors for 7 consecutive days. Participants also noted their daily use of light-emitting devices before bedtime. Endogenous circadian phase was estimated with the dim light melatonin onset (DLMO) in the laboratory. The amplitude of the light-dark cycle to which the subjects were exposed was smaller in delayed than in control subjects, and smaller amplitude was associated with a later DLMO. Smaller amplitude was due to both decreased exposure in the daytime and increased exposure at night. Total exposure to blue light, but not to white light, was lower in delayed subjects, possibly due to lower exposure to blue-rich outdoor light. Lower daily exposure to blue light was associated with a later DLMO. Timing of relative increases and decreases of light exposure in relation to endogenous circadian phase was also compared between the 2 groups. In delayed subjects, there was a relatively higher exposure to white and blue light 2 h after DLMO, a circadian time with maximal phase-delaying effect. Delayed participants also had higher exposure to light 8 to 10 h after DLMO, which occurred mostly during their sleep episode but may have some phase-advancing effects. Self-reported use of light-emitting devices before bedtime was higher in delayed than in control subjects and was associated with a later DLMO. This study suggests that individuals complaining of a delayed sleep schedule engage in light-related behaviors favoring a later circadian phase and a later bedtime.

Study Objectives To test whether the sleep-wake cycle disruption in patients hospitalized with traumatic brain injury (TBI) (1) is also found in patients with traumatic injuries other than TBI (non-TBI) and (2) is associated with a weaker or abnormal circadian clock signal. Methods Forty-two non-mechanically ventilated and non-sedated patients hospitalized for moderate-to-severe TBI were compared to 34 non-TBI patients. They wore wrist actigraphs for 9.4 ± 4.2 days, starting 19.3 ± 12.6 days post-injury. Of these, 17 TBI and 14 non-TBI patients had their urine collected every hour for 25 hours, starting 18.3 ± 12.3 days post-injury. We calculated urinary 6-sulfatoxymelatonin concentration to obtain total 24-hour excretion, excretion onset, offset, duration, amplitude, and acrophase. Using Student’s t-tests, we compared groups on actigraphy (daytime activity ratio, nighttime total sleep time, and fragmentation index) and melatonin variables. We investigated associations between melatonin and actigraphy variables using Pearson’s correlations. Results TBI patients had poorer daytime activity ratio (TBI: 77.5 ± 9.4%; non-TBI: 84.6 ± 6.9%), shorter nighttime total sleep time (TBI: 353.5 ± 96.6 min; non-TBI: 421.2 ± 72.2 min), and higher fragmentation index (TBI: 72.2 ± 30.0; non-TBI: 53.5 ± 23.6) (all p-values < 0.01). A melatonin rhythm was present in both groups, and no group differences were found on melatonin variables. No associations were found between melatonin and actigraphy variables in TBI patients. Conclusion Moderate-to-severe TBI patients have more serious sleep-wake disturbances than non-TBI patients hospitalized in the same environment, suggesting that the brain injury itself alters the sleep-wake cycle. Despite their deregulated 24-hour sleep-wake cycle, TBI patients have a normal circadian clock signal.

Beyond its essential visual role, light, and particularly blue light, has numerous non-visual effects, including stimulating cognitive functions and alertness. Non-visual effects of light may decrease with aging and contribute to cognitive and sleepiness complaints in aging. However, both the brain and the eye profoundly change in aging. Whether the stimulating effects light on cognitive brain functions varies in aging and how ocular changes may be involved is not established. We compared the impact of blue and orange lights on non-visual cognitive brain activity in younger (23.6 ± 2.5 years), and older individuals with their natural lenses (NL; 66.7 ± 5.1 years) or with intraocular lens (IOL) replacement following cataract surgery (69.6 ± 4.9 years). Analyses reveal that blue light modulates executive brain responses in both young and older individuals. Light effects were, however, stronger in young individuals including in the hippocampus and frontal and cingular cortices. Light effects did not significantly differ between older-IOL and older-NL while regression analyses indicated that differential brain engagement was not underlying age-related differences in light effects. These findings show that, although its impact decreases, light can stimulate cognitive brain activity in aging. Since lens replacement did not affect light impact, the brain seems to adapt to the progressive decrease in retinal light exposure in aging.

In chronic obstructive pulmonary disease (COPD), there is large individual variability in the progression of the disease. Low amplitude of rest–activity rhythms has been associated with worse prognosis in a variety of diseases, but it has not been investigated in COPD. The first aim of this exploratory study was to compare disease severity and prognosis indicators between COPD patients with relatively high or low amplitude of their rest–activity cycle, as measured with actigraphy. As a second objective, 24-hour profiles of both activity levels and nighttime-sleep quality were compared between the two subgroups to assess the relative contribution of day- and night-activity levels to high and low rest–activity rhythm amplitude in this population. Rest–activity rhythms were measured with 8–14 days of wrist actigraphy in 14 patients (nine men), aged 58–79 years, suffering from moderate-to-severe COPD. Relative amplitude of 24-hour activity profiles ranged from 0.72 to 0.98. Participants were divided at the median into high-amplitude (mean ± standard deviation 0.9±0.04) and low-amplitude (0.79±0.05) subgroups. There was no significant difference between the two subgroups for pulmonary function or exercise capacity. However, the low-amplitude group had more severe symptoms of dyspnea and worse prognostic scores than the high-amplitude group (P

A shallow ice core was extracted at the summit of Mera Peak at 6376 m a.s.l. in the southern flank of the Nepalese Himalaya range. From this core, we reconstructed the seasonal deposition fluxes of dust and refractory black carbon (rBC) since 1999. This archive presents well preserved seasonal cycles based on a monsoonal precipitation pattern. According to the seasonal precipitation regime in which 80% of annual precipitation falls between June and September, we estimated changes in the concentrations of these aerosols in surface snow. The analyses revealed that mass fluxes are a few orders of magnitude higher for dust (10.4 ± 2.8 g m−2 yr−1 than for rBC (7.9 ± 2.8 mg m−2 yr−1). The relative lack of seasonality in the dust record may reflect a high background level of dust inputs, whether from local or regional sources. Over the 10-year record, no deposition flux trends were detected for any of the species of interest. The data were then used to simulate changes in the surface snow albedo over time and the potential melting caused by these impurities. Mean potential melting caused by dust and rBC combined was 713 kg m−2 yr−1, and for rBC alone, 342 kg m−2 yr−1 for rBC under certain assumptions. Compared to the melting rate measured using the mass and energy balance at 5360 m a.s.l. on Mera Glacier between November 2009 and October 2010, i.e. 3000 kg m−2 yr−1 and 3690 kg m−2 yr−1 respectively, the impact of rBC represents less than 16% of annual potential melting while the contribution of dust and rBC combined to surface melting represents a maximum of 26%. Over the 10-year period, rBC variability in the ice core signal primarily reflected variability of the monsoon signal rather than variations in the intensity of emissions.

The discovery of intrinsically photosensitive retinal ganglion cells (ipRGCs) marked a major shift in our understanding of how light is processed by the mammalian brain. These ipRGCs influence multiple functions not directly related to vision such as the synchronization of circadian rhythmicity, pupil constriction, the regulation of alertness and sleep, as well as the modulation of cognition. More recently, it was demonstrated that ipRGCs may also contribute to basic visual functions. The impact of ipRGCs on visual functions, independently of image forming photoreceptors, remains however difficult to isolate, particularly in humans. We previously showed that exposure to intense monochromatic blue light (465nm) induced awareness of light in a forced choice task in three rare totally visually blind individuals without detectable rod and cone function, but who retained non-visual responses to light, very likely via ipRGCs. The neural foundation of such light awareness in the absence of conscious vision is unknown, however. In this study, we characterized the brain activity of these three rare participants using electroencephalography (EEG), and demonstrate that unconsciously perceived light triggers an early and reliable transient desynchronization (i.e. decreased power) of the alpha EEG rhythm (8-14 Hz) over the occipital cortex. These results provide compelling insight into how ipRGC may contribute to transient changes in ongoing brain activity. They suggest that occipital alpha rhythm synchrony, which is typically linked to the visual system, is modulated by ipRGCs photoreception; a process that may contribute to the awareness of light in those blind individuals.

Objective: To investigate whether the progressive recuperation of consciousness was associated with the reconsolidation of sleep and wake states in hospitalized patients with acute traumatic brain injury (TBI). Methods: This study comprised 30 hospitalized patients (age 29.1 6 13.5 years) in the acute phase of moderate or severe TBI. Testing started 21.0 6 13.7 days postinjury. Consciousness level and cognitive functioning were assessed daily with the Rancho Los Amigos scale of cognitive functioning (RLA). Sleep and wake cycle characteristics were estimated with continuous wrist actigraphy. Mixed model analyses were performed on 233 days with the RLA (fixed effect) and sleep-wake variables (random effects). Linear contrast analyses were performed in order to verify if consolidation of the sleep and wake states improved linearly with increasing RLA score. Results: Associations were found between scores on the consciousness/cognitive functioning scale and measures of sleep-wake cycle consolidation (p , 0.001), nighttime sleep duration (p 5 0.018), and nighttime fragmentation index (p , 0.001). These associations showed strong linear relationships (p , 0.01 for all), revealing that consciousness and cognition improved in parallel with sleep-wake quality. Consolidated 24-hour sleep-wake cycle occurred when patients were able to give context-appropriate, goal-directed responses. Conclusions: Our results showed that when the brain has not sufficiently recovered a certain level of consciousness, it is also unable to generate a 24-hour sleep-wake cycle and consolidated nighttime sleep. This study contributes to elucidating the pathophysiology of severe sleepwake cycle alterations in the acute phase of moderate to severe TBI., This study was supported by the Canadian Institutes of Health Research (grant no. 115172) and by the Fonds pour la Recherche du Québec–Santé (grant no. 24742).

Objective To assess factors that might contribute to a delayed sleep schedule in young adults with sub-clinical features of delayed sleep phase disorder. Methods Two groups of 14 young adults (eight women) were compared: one group complaining of a delayed sleep schedule and a control group with an earlier bedtime and no complaint. For one week, each subject maintained a target bedtime reflecting their habitual sleep schedule. Subjects were then admitted to the laboratory for the assessment of circadian phase (dim light melatonin onset), subjective sleepiness, and non-visual light sensitivity. All measures were timed relative to each participant's target bedtime. Non-visual light sensitivity was evaluated using subjective sleepiness and salivary melatonin during 1.5-h exposure to blue light, starting one hour after target bedtime. Results Compared to control subjects, delayed subjects had a later circadian phase and a slower increase of subjective sleepiness in the late evening. There was no group difference in non-visual sensitivity to blue light, but we found a positive correlation between melatonin suppression and circadian phase within the delayed group. Conclusions Our results suggest that a late circadian phase, a slow build-up of sleep need, and an increased circadian sensitivity to blue light contribute to the complaint of a delayed sleep schedule. These findings provide targets for strategies aiming to decreasing the severity of a sleep delay and the negative consequences on daytime functioning and health.

Background. Sleep-wake disturbances are among the most persistent sequelae after traumatic brain injury (TBI) and probably arise during the hospital stay following TBI. These disturbances are characterized by difficulties sleeping at night and staying awake during the day. Objective. The aim of the present study was to document rest-activity cycle consolidation in acute moderate/severe TBI using actigraphy and to assess its association with injury severity and outcome. Methods. In all, 16 hospitalized patients (27.1 ± 11.3 years) with moderate/severe TBI wore actigraphs for 10 days, starting in the intensive care unit (ICU) when continuous sedation was discontinued and patients had reached medical stability. Activity counts were summed for daytime (7:00-21:59 hours) and nighttime periods (22:00-6:59 hours). The ratio of daytime period activity to total 24-hour activity was used to quantify rest-activity cycle consolidation. An analysis of variance was carried out to characterize the evolution of the daytime activity ratio over the recording period. Results. Rest-activity cycle was consolidated only 46.6% of all days; however, a significant linear trend of improvement was observed over time. Greater TBI severity and longer ICU and hospital lengths of stay were associated with poorer rest-activity cycle consolidation and evolution. Patients with more rapid return to consolidated rest-activity cycle were more likely to have cleared posttraumatic amnesia and have lower disability at hospital discharge. Conclusions. Patients with acute moderate/severe TBI had an altered rest-activity cycle, probably reflecting severe fragmentation of sleep and wake episodes, which globally improved over time. A faster return to rest-activity cycle consolidation may predict enhanced brain recovery.

The purpose of this pilot study was to determine the impact of time of day on the acute response to incremental exercise in chronic obstructive pulmonary disease (COPD). Fourteen subjects (nine men) aged 71 ± 7 years with moderate to severe airflow obstruction (FEV1: 58 ± 13% predicted) followed a counterbalanced randomized design, performing three symptom-limited incremental cycling tests at 8:00, 12:00, and 16:00 hours on different days, each preceded by a spirometry. COPD medications were withdrawn prior to testing. No overall time effect was found for peak exercise capacity (p = 0.22) or pulmonary function (FEV1, p = 0.56; FVC, p = 0.79). However, a large effect size (f = 0.48) was observed for peak exercise capacity and several pulmonary function parameters. For peak exercise capacity, the average within-subject coefficient of variation was 5.5 ± 3.9% and the average amplitude of change was 7 ± 5W. Seven subjects (50%) showed diurnal changes at levels equal to or beyond the minimal clinically important difference for both peak exercise capacity and pulmonary function. In this sub-group, peak exercise capacity was greatest at 16:00 hours (p = 0.03, ƒ = 1.04). No systematic time-of-day effect on peak exercise capacity was obtained in COPD patients in the present pilot study. However, based on the observed effect size and on the average amplitude of change and within-subject variations seen across testing times, the guidelines recommendation that time of day be standardized for repeat exercise testing in COPD should be maintained.

Purpose: The aim of this study was to investigate the association between depressive symptoms severity and amplitude of diurnal variations in depression symptoms in patients with chronic obstructive pulmonary disease (COPD). Design: Prospective, observational proof-of-concept study. Methods: Fourteen participants with moderate/severe COPD completed a 20-item Center for Epidemiologic Studies Depression Scale (CES-D) estimating depressive symptoms severity. Throughout one week, the four-item very short version of the CES-D was completed every day in the morning, afternoon, and evening. Findings: Strong positive correlations were observed between depressive severity and the mean range of diurnal variations in positive (r = .61) and depressed affects (r = .67), somatic complaints (r = .82), and disturbed interpersonal relationships (r = .71). Conclusion: In COPD patients, a greater diurnal variation in depression symptoms was associated with greater depression severity. This relationship seems independent of COPD severity. Clinical Relevance: Diurnal variation in the symptoms of depression is a new method of identifying depression severity in COPD.

In plants, 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) is a monosaccharide that is only found in the cell wall pectin, rhamnogalacturonan-II (RG-II). Incubation of 4-day-old light-grown Arabidopsis seedlings or tobacco BY-2 cells with 8-azido 8-deoxy Kdo (Kdo-N3 ) followed by coupling to an alkyne-containing fluorescent probe resulted in the specific in muro labelling of RG-II through a copper-catalysed azide-alkyne cycloaddition reaction. CMP-Kdo synthetase inhibition and competition assays showing that Kdo and D-Ara, a precursor of Kdo, but not L-Ara, inhibit incorporation of Kdo-N3 demonstrated that incorporation of Kdo-N3 occurs in RG-II through the endogenous biosynthetic machinery of the cell. Co-localisation of Kdo-N3 labelling with the cellulose-binding dye calcofluor white demonstrated that RG-II exists throughout the primary cell wall. Additionally, after incubating plants with Kdo-N3 and an alkynated derivative of L-fucose that incorporates into rhamnogalacturonan I, co-localised fluorescence was observed in the cell wall in the elongation zone of the root. Finally, pulse labelling experiments demonstrated that metabolic click-mediated labelling with Kdo-N3 provides an efficient method to study the synthesis and redistribution of RG-II during root growth.

Background Sleep-wake disturbances are frequently reported following traumatic brain injury (TBI), but they remain poorly documented in the acute stage of injury. Little is known about their origin and evolution. Case presentation This study presents the case of a patient in the acute phase of a severe TBI. The patient was injured at work when falling 12 m into a mine and was hospitalized in the regular wards of a level I trauma centre. From days 31 to 45 post-injury, once he had reached a level of medical stability and continuous analgosedation had been ceased, his sleep-wake cycle was monitored using actigraphy. Results showed significant sleep-wake disturbances and severe sleep deprivation. Indeed, the patient had an average nighttime sleep efficiency of 32.7 ± 15.4 %, and only an average of 4.8 ± 1.3 h of sleep per 24-h period. After hospital discharge to the rehabilitation centre, where he remained for 5 days, the patient was readmitted to the same neurological unit for paranoid delusions. During his second hospital stay, actigraphy recordings resumed from days 69 to 75 post-injury. A major improvement in his sleep-wake cycle was observed during this second stay, with an average nighttime sleep efficiency of 96.3 ± 0.9 % and an average of 14.1 ± 0.9 h of sleep per 24-h period. Conclusion This study is the first to extensively document sleep-wake disturbances in both the acute and subacute phases of severe TBI. Results show that prolonged sleep deprivation can be observed after TBI, and suggest that the hospital environment only partially contributes to sleep-wake disturbances. Continuous actigraphic monitoring may prove to be a useful clinical tool in the monitoring of patients hospitalized after severe TBI in order to detect severe sleep deprivation requiring intervention. The direct impact of sleep-wake disturbances on physiological and cognitive recovery is not well understood within this population, but is worth investigating and improving. Electronic supplementary material The online version of this article (doi:10.1186/s12883-016-0709-x) contains supplementary material, which is available to authorized users.

In most situations, complete circadian adjustment is not recommended for night workers. With complete adjustment, workers experience circadian misalignment when returning on a day-active schedule, causing repeated circadian phase shifts and internal desynchrony. For this reason, partial circadian realignment was proposed as a good compromise to stabilize internal circadian rhythms in night shift workers. However, the extent of partial circadian adjustment necessary to improve sleep and vigilance quality is still a matter of debate. In this study, the effects of small but statistically significant partial circadian adjustments on sleep and vigilance quality were assessed in a laboratory simulation of night work to determine whether they were also of clinical significance. Partial adjustments obtained by phase delay or by phase advance were quantified not only by the phase shift of dim light salivary melatonin onset, but also by the overlap of the episode of melatonin production with the sleep-wake cycle adopted during simulated night work. The effects on daytime sleep and night-time vigilance quality were modest. However, they suggest that even small adjustments by phase delay may decrease the accumulation of sleep debt, whereas the advance strategy improves subjective alertness and mood during night work. Furthermore, absolute phase shifts, by advance or by delay, were associated with improved subjective alertness and mood during the night shift. These strategies need to be tested in the field, to determine whether they can be adapted to real-life situations and provide effective support to night workers.

Decreased melatonin production, due to acute suppression of pineal melatonin secretion by light exposure during night work, has been suggested to underlie higher cancer risks associated with prolonged experience of night work. However, the association between light exposure and melatonin production has never been measured in the field. In this study, 24-h melatonin production and ambulatory light exposure were assessed during both night-shift and day/evening-shift periods in 13 full-time rotating shiftworkers. Melatonin production was estimated with the excretion of urinary 6-sulfatoxymelatonin (aMT6s), and light exposure was measured with an ambulatory photometer. There was no difference in total 24-h aMT6s excretion between the two work periods. The night-shift period was characterized by a desynchrony between melatonin and sleep-wake rhythms, as shown by higher melatonin production during work and lower melatonin production during sleep when working night shifts than when working day/evening shifts. Light exposure during night work showed no correlation with aMT6s excreted during the night of work (p .5), or with the difference in 24-h aMT6s excretion between the two work periods (p .1). However, light exposure during night work was negatively correlated with total 24-h aMT6s excretion over the entire night-shift period (p .01). In conclusion, there was no evidence of direct melatonin suppression during night work in this population. However, higher levels of light exposure during night work may have decreased total melatonin production, possibly by initiating re-entrainment and causing internal desynchrony. This interpretation is consistent with the proposition that circadian disruption, of which decreased melatonin production is only one of the adverse consequences, could be the mediator between night shiftwork and cancer risks.

Background and Objectives. The onset of pervasive sleep-wake disturbances associated with traumatic brain injury (TBI) is poorly understood. This study aimed to ( a) determine the feasibility of using polysomnography in patients in the acute, hospitalized stage of severe TBI and ( b) explore sleep quality and sleep architecture during this stage of recovery, compared to patients with other traumatic injuries. Methods. A cross-sectional case-control design was used. We examined the sleep of 7 patients with severe TBI (17-47 years; 20.3 ± 15.0 days postinjury) and 6 patients with orthopedic and/or spinal cord injuries (OSCI; 19-58 years; 16.9 ± 4.9 days postinjury). One night of ambulatory polysomnography was performed at bedside. Results. Compared to OSCI patients, TBI patients showed a significantly longer duration of nocturnal sleep and earlier nighttime sleep onset. Sleep efficiency was low and comparable in both groups. All sleep stages were observed in both groups with normal proportions according to age. Conclusion. Patients in the acute stage of severe TBI exhibit increased sleep duration and earlier sleep onset, suggesting that the injured brain enhances sleep need and/or decreases the ability to maintain wakefulness. As poor sleep efficiency could compromise brain recovery, further studies should investigate whether strategies known to optimize sleep in healthy individuals are efficacious in acute TBI. While there are several inherent challenges, polysomnography is a useful means of examining sleep in the early stage of recovery in patients with severe TBI.

Background Vulnerability to the reduction in natural light associated with fall/winter is generally accepted as the main trigger of seasonal affective disorder (SAD), whereas light therapy is a treatment of choice of the disorder. However, the relationship between exposure to light and mood regulation remains unclear. As compared with green light, blue light was shown to acutely modulate emotion brain processing in healthy individuals. Here, we investigated the impact of light on emotion brain processing in patients with SAD and healthy control subjects and its relationship with retinal light sensitivity. Methods Fourteen symptomatic untreated patients with SAD (34.5 ± 8.2 years; 9 women) and 16 healthy control subjects (32.3 ± 7.7 years; 11 women) performed an auditory emotional task in functional magnetic resonance imaging during the fall/winter season, while being exposed to alternating blue and green monochromatic light. Scotopic and photopic retinal light sensitivities were then evaluated with electroretinography. Results Blue light enhanced responses to auditory emotional stimuli in the posterior hypothalamus in patients with SAD, whereas green light decreased these responses. These effects of blue and green light were not observed in healthy control subjects, despite similar retinal sensitivity in SAD and control subjects. Conclusions These results point to the posterior hypothalamus as the neurobiological substrate involved in specific aspects of SAD, including a distinctive response to light and altered emotional responses.

Background A close temporal relationship was shown between the onset of melatonin secretion at night and the worsening of restless legs syndrome (RLS) symptoms, suggesting that melatonin may play a role in the genesis of this phenomenon. To test this hypothesis we studied the effects of the administration of exogenous melatonin and, conversely, the suppression of endogenous melatonin secretion by bright light exposure on the severity of RLS symptoms. Methods Eight RLS subjects were studied in three conditions: at baseline, after administration of melatonin and during bright light exposure. The severity of RLS symptoms was assessed by the suggested immobilization test (SIT), which allows quantification of both sensory and motor manifestations (SIT-PLM) of RLS. Results Analyses showed a significant increase of SIT-PLM index when subjects received exogenous melatonin compared to both baseline and bright light conditions, but bright light exposure had no effect on leg movements compared to the baseline condition. Analyses also revealed a small but significant decrease in sensory symptoms with bright light exposure compared to baseline. Conclusion Exogenous melatonin may have a detrimental effect on motor symptoms, and bright light exposure produced small but significant improvement of leg discomfort. The study shows the interest of using the SIT to measure outcome of intervention in RLS. Further studies will be needed to assess the therapeutic value of bright light in RLS.

INSOMNIA REFERS TO THE SUBJECTIVE EXPERIENCE OF NON RESTORATIVE SLEEP DUE TO DIFFICULTY FALLING ASLEEP, DIFFICULTY MAINTAINING SLEEP or early awakening.1,2 Insomnia is the most common sleep complaint in the general population, with a variable prevalence ranging from 2% to 48%, a broad range which reflects the variable definition of insomnia, different modalities of investigation, and the population under study.2,3 Indeed, insomnia may appear in association with another medical or psychiatric disorder (comorbid insomnia), or as an independent condition as primary insomnia.3 Hallmarks of primary insomnia are the subjective experience of difficulty initiating and maintaining sleep, accompanied by distress or impairment in daytime function; the repetitive (as opposed to sporadic) recurrence of a poor sleep night;4 and duration of ≥ 1 month (according to DSM-IV definition)5, whereas ≥ 6 months duration is required to fulfill diagnostic criteria for chronic insomnia.1–3 The pathophysiological mechanisms of primary insomnia remain elusive. Psychophysiological factors such as stress, anxiety, and autonomic hyperarousal are significant components of this condition6 and would appear to be implicated in its genesis and perpetuation. Polysomnography often fails to detect traditional criteria of poor sleep in insomniacs.2 However, studies assessing quantitative electroencephalographic (EEG) spectral analysis have shown that, even in the presence of an apparently normal sleep architecture during polysomnography, these subjects have a decrease in EEG activity in the low frequencies (0.5-3.5 Hz) and an increased activity in high frequencies (14-45 Hz) during NREM sleep,7–9 suggesting hyperactivity of the central nervous system during their sleep. Finally, studies using positron emission tomography assessing metabolic activity during NREM sleep have documented that insomniacs, compared to good sleepers, have higher metabolic activity in the ascending reticular activating system, along with areas pertaining to the emotion regulation and cognitive systems.10 These data suggest that the interaction of the systems regulating arousal, emotions, and cognitive function is part of the neurobiology of insomnia and support the concept that poor sleep is a symptom of a primary disorder of the arousal system. Indeed, as part of the arousal response, nocturnal plasma catecholamine concentration11 and low frequency components of heart rate variability have been reported to be higher in insomniacs than good sleepers.12 Insomnia significantly impairs daytime function and predisposes to major depression.1,3 There is also an emerging epidemiological evidence linking insomnia to higher cardiovascular morbidity and mortality.13–17 However, at present, no studies have assessed the effects of insomnia on cardiovascular function, and to our knowledge, no data exist on nighttime BP, which has been shown to be relevant in assessing cardiovascular risk in recent large studies.18,19 Blood pressure physiologically decreases during sleep,20 a reduction commonly called dipping. Studies indicated that day-to-night and nighttime regulation of BP appear to be tightly coupled with autonomic changes occurring during the wake-sleep cycle.21,22 This suggests that BP should be particularly sensitive to disturbances occurring during sleep, especially in the presence of hyperactivation of the sympathetic nervous system, such as that which may occur in insomniacs. In the present study we investigated the 24-hour profile of arterial BP in subjects with chronic primary insomnia and tested the hypothesis that these subjects have higher nighttime BP and an attenuation of nocturnal BP dipping compared to good sleepers. We also assessed the relationship existing between nighttime BP and polysomnographic measures of poor sleep and EEG power spectra in the β frequencies.

In addition to being necessary for vision, light also plays a primary role in circadian physiology. Humans are diurnal animals and their biological clock synchronizes their physiological functions in such a way that functions associated with activity happen in the daytime while functions associated with rest occur at night. A misalignment between the endogenous circadian clock and the desired sleep schedule is the main cause of circadian sleep disorders; it may be involved in certain mood disorders as well. Since light is the main environmental cue used by the biological clock to set its own timing in relation to the day-night cycle, inappropriate light exposure can be involved in the physiopathology of circadian disorders. Conversely, when handled properly, controlled light exposure can be used to treat some mood and sleep disorders. While the earliest studies in the field focused solely on exposure to bright light, contemporary studies aim at understanding how the entire profile of light-dark exposure can influence the circadian clock and, consequently, mood, sleep, and vigilance quality. Following a brief summary of the main concepts underlying the non-visual effects of light, this paper presents some studies using ambulatory measurements of light exposure to illustrate how these concepts apply in real-life situations and discusses the clinical relevance of light exposure in the natural environment for mood, sleep, and circadian disorders.

Circadian types classify individuals according to their preferred timing for activity and sleep, morning and evening types showing, respectively, early or late preferences. This characteristic has been associated with corresponding differences in circadian sleep propensity. In this study, quantitative analysis of the sleep EEG in antero-posterior derivations was used to test the hypothesis that morning and evening types differ not only in the circadian aspect of sleep regulation but also in the homeostatic aspect. Morning types and evening types (six men and six women per group, aged 19-34 years) were selected using the Morningness-Eveningness Questionnaire. They were studied by polysomnography according to their preferred sleep schedule. Spectral activity in four midline derivations (Fz, Cz, Pz, Oz) was calculated separately in nonrapid eye movement (NREM) sleep and in rapid eye movement (REM) sleep. In NREM sleep, morning types showed a steeper decrease of slow-wave activity (SWA; 1-5 Hz) per sleep cycle in the fronto-central derivations and a steeper increase in 13-14 Hz activity in the parieto-occipital derivations than did evening types. Nonlinear regression analysis revealed that the exponential decay rate of relative values of SWA in NREM sleep was faster in morning than evening types, in the frontal derivation. In REM sleep, morning types showed a steeper decrease of high sigma (14-16 Hz) and beta (16-24 Hz) activities across the night in centro-parietal derivations than did evening types. These results show for the first time a clear difference between morning types and evening types in homeostatic sleep regulation.

The mechanisms underlying age-related changes in the signal from the biological clock have yet to be determined. The authors sought to determine if the phase advance of circadian melatonin rhythm during the middle years of life is related to different patterns of habitual light exposure. Forty-one healthy subjects between the ages of 22 and 58 y were studied. Habitual light exposure was measured by a wrist monitor for 7 days. Participants underwent a 25-h constant routine. They provided saliva samples every 30 min, and melatonin concentration was determined by radioimmunoassay to assess salivary dim light melatonin onset (S-DLMO1.3). Aging was associated with earlier S-DLMO1.3. Increasing age was not related to the time spent at different light intensities. However, it was associated with lower percentage of light exposure during the night (between 0200-0400, 0600-0700, and 2300-2400 h) and with higher percentage of light exposure in the morning (between 0800-1100 h). Earlier S-DLMO1.3 was associated with lower percentage of light exposure early on in the night (between 2200-0000, 0000-0100, and 0200-0300 h) as well as in the afternoon (between 1500-1600 h) and with higher percentage of light exposure in the morning (between 0800-1100 h). When the effects of age were controlled, there was no significant relationship between S-DLMO1.3 and percentages of light exposure. Yet increasing age was associated with earlier S-DLMO1.3 regardless of light exposure patterns. Earlier habitual wake time explained the earlier light exposure patterns of older subjects. Both habitual wake time and age contributed to the prediction of S-DLMO1.3. The results suggest a phase advance of circadian rhythms in the middle years of life. Whereas a clear change in habitual light exposure patterns was associated with aging and with shifts in S-DLMO1.3, it did not explain entirely the age-related advance of melatonin circadian phase.

In this article the authors report insights into autism developed through their extensive experience of psychoanalytic therapy with children with autism. The first stages of body psychic development are seriously disrupted by this pathology, resulting in primitive anxieties of falling and of being liquefied. These anxieties are connected to the fragile development of body ego and of its related spatiotemporal organisation. The changes in children observed by the authors during the therapeutic process lead them to offer a psychodynamic assessment tool, which revolves principally around the development of body ego. After the initial state of 'severe autism', the authors describe three stages: the stage of 'recovery of the skin' (Bick); the established 'symbiotic phase', subdivided into 'vertical then horizontal splitting of the body ego'; and finally the stage of 'individuation'. First, the authors describe the principal psychoanalytic approaches to autism and reflect on the links possible with non-psychoanalytic work.

A shorter phase angle between habitual wake time and underlying circadian rhythms has been reported in evening types (E types) compared to morning-types (M types). In this study, phase angles were compared between 12 E types and 12 M types to verify if this difference was observed when the sleep schedule was relatively free from external social constraints. Subjects were selected according to their Morningness-Eveningness Questionnaire score (MEQ score). There were 6 men and 6 women in each group (ages 19-34 years), and all had a habitual sleep duration between 7 and 9 h. Sleep schedule was recorded by actigraphy and averaged over 7 days. Circadian phase was estimated by the hour of temperature minimum (Tmin) in a 26-h recording and by the timing of the onset of melatonin secretion (dim-light melatonin onset [DLMO]) measured in saliva samples. Phase angles were defined as the interval between phase markers and averaged wake time. Results showed that, in the present experimental conditions, phase angles were very similar in the 2 groups of subjects. However, results confirmed the previously reported correlation between phase and phase angle, showing that a later circadian phase was associated with a shorter phase angle. Gender comparisons showed that for a same MEQ score, women had an earlier DLMO and a longer phase angle between DLMO and wake time. Despite a significant difference in the averaged circadian phases between E-type and M-type groups, there was an overlap in the circadian phases of the subjects of the 2 groups. Further comparisons were made between the 2 circadian types, separately for the subgroups with overlapping or nonoverlapping circadian phases. In both subgroups, the significant difference between MEQ scores, bedtimes, and wake times were maintained in the expected direction. In the subgroup with nonoverlapping circadian phases, phase angles were shorter in E-type subjects, in accordance with previous studies. However, in the overlapping subgroup, phase angles were significantly longer in E types compared to M types. Results suggest that the morningness-eveningness preference identified by the MEQ score refers to 2 distinct mechanisms, 1 associated with a difference in circadian period and phase of entrainment and the other associated with chronobiological aspects of sleep regulation.

Recently, it was suggested that the intensity of restless legs syndrome (RLS) symptoms may be modulated by a circadian factor. The objective of this study was to evaluate, during a 28-hour modified constant routine, the nycthemeral or circadian variations in subjective leg discomfort and periodic leg movements (PLMs) and to parallel these changes with those of subjective vigilance, core body temperature, and salivary melatonin. Seven patients with primary RLS and seven healthy subjects matched for sex and age entered this study. Although the symptoms were more severe in patients than in controls, a significant circadian variation in leg discomfort and PLM (p < 0.01) was found for both groups. In both groups, the profiles of leg discomfort and PLM were significantly correlated with those of subjective vigilance, core body temperature, and salivary melatonin. However, among these variables, the changes in melatonin secretion were the only ones that preceded the increase in sensory and motor symptoms in RLS patients. This result and those of others studies showing that melatonin exerts an inhibitory effect on central dopamine secretion suggest that melatonin might be implicated in the worsening of RLS symptoms in the evening and during the night.

Health care professionals have a duty to provide the best services available to their clients. Clinical practice guidelines (CPGs) can help physiotherapists do so by providing them with access to clinical recommendations for evaluating and treating various conditions. The purpose of this study was twofold: to assess the quality of existing CPGs in physiotherapy and to create a Web-based inventory of these CPGs. Nine guidelines were selected (consisting of 61 recommendation statements) according to predetermined inclusion/exclusion criteria and then independently quality assessed by four appraisers using the AGREE (Appraisal of Guidelines for Research and Evaluation) Instrument. The methodological quality of these musculoskeletal CPGs was fair (mean quality score of 46.6%; range 0%–83%; [95% confidence interval {CI} 17.0%–70.5%]) depending on the specific AGREE dimension.

With progressively brighter stimuli, the amplitude of the photopic b-wave first increases, briefly saturates and then decreases gradually to reach a plateau, where the amplitude of the b-wave equals that of the a-wave; a phenomenon previously presented as the photopic hill. The unique presentation of this luminance-response function seriously complicates its analysis with curve fitting equations such as that of Naka–Rushton used for scotopic electroretinogram. We report a method of analysis of the photopic hill based on easily identifiable and reproducible features of the ascending and descending limbs of this function. The clinical usefulness of these parameters is illustrated with selected cases of retinal disorders.

Fourteen healthy subjects (8 women, 6 men, aged 22-35 yr) were recruited. Each subject was exposed, in a counterbalanced order, to bright white light (BWL: 3000 lux) and to dim red light (DRL

Background: An anomaly in the retinal adaptation processes to the decreased light exposure in winter has been suggested as a contributing factor in winter depression. The purpose of this study was to investigate seasonal variations in rod sensitivity in normal subjects and in subjects with seasonal mood variations. Methods: Nine normal subjects (5 men, 4 women, aged 21–28 years) and 12 subjects with subsyndromal seasonal affective disorder (S-SAD)(3 men, 9 women, aged 21–44 years) were selected based on their global seasonality score (GSS) from the Seasonal Pattern Assessment Questionnaire. Scotopic electroretinograms (ERGs) were obtained once in winter and once in summer. Retinal sensitivity, which represents a relative threshold, was obtained from the rod ERG luminance–response functions. Results: A difference in retinal sensitivity between the two groups appeared only in the winter with lower retinal sensitivity found in the S-SAD group. A positive correlation between the GSS and the magnitude of the winter decrease in rod sensitivity was also observed. Limitations: The S-SAD subjects studied in this research did not receive a formal psychiatric evaluation. This will be necessary in future studies to determine if the changes in retinal sensitivity are specific to seasonal affective disorders. In addition, in the present study, the differences in age and gender between the two groups limit the interpretation of the possible contribution of these two parameters to the results. Conclusion: The seasonal changes in retinal sensitivity that parallel seasonal mood variations suggest that the ERG may represent a useful tool to investigate seasonal affective disorders.

Decreased melatonin production, due to nighttime exposure to light, has been proposed as one of the physiological mechanisms increasing cancer risk in night workers. However, few studies measured melatonin production in night workers, and most of these studies did not measure melatonin over 24 h. One study compared total melatonin production between day and night shifts in rotating night workers and did not find significant differences. However, without baseline measures, it was not possible to exclude that melatonin production was reduced during both day and night work. Here, we used data collected in a simulation study of night work to determine the effect of night work on both nighttime and 24-h melatonin production, during three consecutive days of simulated night work. Thirty-eight healthy subjects (15 men, 23 women; 26.6 ± 4.2 years) participated in a 6-d laboratory study. Circadian phase assessments were made with salivary dim light melatonin onset (DLMO) on the first and last days. Simulated day work (09:00-17:00 h) occurred on the second day, followed by three consecutive days of simulated night work (00:00-08:00 h). Light intensity at eye level was set at 50 lux during both simulated day and night work. The subjects were divided into three matched groups exposed to specific daytime light profiles that produced various degrees of circadian phase delays and phase advances. Melatonin production was estimated with the excretion of urinary 6-sulfatoxymelatonin (aMT6s). For the entire protocol, urine was collected every 2 h, except for the sleep episodes when the interval was 8 h. The aMT6s concentration in each sample was multiplied by the urine volume and then added to obtain total aMT6s excretion during nighttime (00:00-08:00 h) and during each 24-h day (00:00-00:00 h). The results showed that melatonin production progressively decreased over consecutive days of simulated night work, both during nighttime and over the 24 h. This decrease was larger in women using oral contraceptives. There was no difference between the three groups, and the magnitude of the decrease in melatonin production for nighttime and for the 24 h was not associated with the magnitude of the absolute circadian phase shift. As light intensity was relatively low and because the decrease in melatonin production was progressive, direct suppression by nighttime light exposure was probably not a significant factor. However, according to previous experimental observations, the decrease in melatonin production most likely reflects the circadian disruption associated with the process of re-entrainment. It remains to be determined whether reduced melatonin production can be harmful by itself, but long-term and repeated circadian disruption most probably is.

Study Objectives: Light exposure, particularly blue light, is being recognized as a potent mean to stimulate alertness and cognition in young individuals. Aging is associated with changes in alertness regulation and cognition. Whether the effect of light on cognitive brain function changes with aging is unknown, however. Design: Cross-sectional study. Setting: Functional Neuroimaging Unit, University of Montreal Geriatric Institute. Participants: Sixteen younger (23 ± 4.1 y) and 14 older (61 ± 4.5 y) healthy participants were recruited in the current study. Intervention: Blue light administration. Measurements: We used functional magnetic resonance imaging to record brain responses to an auditory working memory task in young and older healthy individuals, alternatively maintained in darkness or exposed to blue light. Results: Results show that the older brain remains capable of showing sustained responses to light in several brain areas. However, compared to young individuals, the effect of blue light is decreased in the pulvinar, amygdala, and tegmentum as well as in the insular, prefrontal, and occipital cortices in elderly individuals. Conclusion: The effect of blue light on brain responses diminishes with aging in areas typically involved in visual functions and in key regions for alertness regulation and higher executive processes. Our findings provide the first indications that the effect of light on cognition may be reduced in healthy aging.

International audience; BACKGROUND AND AIMSRhamnogalacturonan-II (RG-II) is one of the pectin motifs found in the cell wall of all land plants. It contains sugars such as 2-keto-3-deoxy-d-lyxo-heptulosaric acid (Dha) and 2-keto-3-deoxy-d-manno-octulosonic acid (Kdo), and within the wall RG-II is mostly found as a dimer via a borate diester cross-link. To date, little is known regarding the biosynthesis of this motif. Here, after a brief review of our current knowledge on RG-II structure, biosynthesis and function in plants, this study explores the implications of the presence of a Golgi-localized sialyltransferase-like 2 (SIA2) protein that is possibly involved in the transfer of Dha or Kdo in the RG-II of Arabidopsis thaliana pollen tubes, a fast-growing cell type used as a model for the study of cell elongation.METHODS:Two heterozygous mutant lines of arabidopsis (sia2-1+/- and qrt1 × sia2-2+/-) were investigated. sia2-2+/- was in a quartet1 background and the inserted T-DNA contained the reporter gene β-glucuronidase (GUS) under the pollen-specific promoter LAT52. Pollen germination and pollen tube phenotype and growth were analysed both in vitro and in vivo by microscopy.KEY RESULTS:Self-pollination of heterozygous lines produced no homozygous plants in the progeny, which may suggest that the mutation could be lethal. Heterozygous mutants displayed a much lower germination rate overall and exhibited a substantial delay in germination (20 h of delay to reach 30 % of pollen grain germination compared with the wild type). In both lines, mutant pollen grains that were able to produce a tube had tubes that were either bursting, abnormal (swollen or dichotomous branching tip) or much shorter compared with wild-type pollen tubes. In vivo, mutant pollen tubes were restricted to the style, whereas the wild-type pollen tubes were detected at the base of the ovary..CONCLUSIONS:This study highlights that the mutation in arabidopsis SIA2 encoding a sialyltransferase-like protein that may transfer Dha or Kdo on the RG-II motif has a dramatic effect on the stability of the pollen tube cell wall.

Light exposure was measured in 30 permanent night nurses to determine if specific light/dark profiles could be associated with a better circadian adaptation. Circadian adaptation was defined as a significant shift in the timing of the episode of melatonin secretion into the daytime. Light exposure was continuously recorded with ambulatory wrist monitors for 56 h, including 3 consecutive nights of work. Participants were then admitted to the laboratory for 24 h where urine was collected every 2 h under dim light for the determination of 6-sulphatoxymelatonin concentration. Cosinor analysis was used to estimate the phase position of the episode of melatonin secretion. Five participants showed a circadian adaptation by phase delay (“delayed participants”) and 3 participants showed a circadian adaptation by phase advance (“advanced participants”). The other 22 participants had a timing of melatonin secretion typical of day-oriented people (“nonshifters”). There was no significant difference between the 3 groups for total light exposure or for bright light exposure in the morning when traveling home. However, the 24-h profiles of light exposure were very distinctive. The timing of the main sleep episode was associated with the timing of light exposure. Delayed participants, however, slept in darker bedrooms, and this had a major impact on their profile of light/dark exposure. Delayed and advanced participants scored as evening and morning types, respectively, on a morningness-eveningness scale. This observation suggests that circadian phase prior to night work may contribute to the initial step toward circadian adaptation, later reinforced by specific patterns of light exposure.

Traumatic brain injury (TBI) is a major health concern in industrialised countries. Sleep and wake disturbances are among the most persistent and disabling sequelae after TBI. Yet, despite the widespread complaints of post-TBI sleep and wake disturbances, studies on their etiology, pathophysiology, and treatments remain inconclusive. This narrative review aims to summarise the current state of knowledge regarding the nature of sleep and wake disturbances following TBI, both subjective and objective, spanning all levels of severity and phases post-injury. A second goal is to outline the various causes of post-TBI sleep-wake disturbances. Globally, although sleep-wake complaints are reported in all studies and across all levels of severity, consensus regarding the objective nature of these disturbances is not unanimous and varies widely across studies. In order to optimise recovery in TBI survivors, further studies are required to shed light on the complexity and heterogeneity of post-TBI sleep and wake disturbances, and to fully grasp the best timing and approach for intervention.

Electroencephalograms (EEGs) of 14 normal subjects were recorded every 2 h during 38 h constant routines. Adjacent narrow frequency bands (NFB) with similar temporal trends were grouped into frequency clusters. Clusters I (2.00-7.75 Hz) and III (11.00-14.75 Hz) exhibited similar time courses which may reflect both the duration of time awake and a circadian modulation. Cluster II (8.00-10.75 Hz) was characterized by a time course similar to the circadian modulation of core body temperature. Cluster V (18.00-24.75 Hz) was correlated with subjective sleepiness and may reflect the increasing effort made by subjects to perform the task as sleep deprivation lengthened. Various NFB in the waking EEG may reflect different physiological mechanisms underlying variations in vigilance states.

This study was designed to test the hypothesis that bright light (BL) can have a stimulating effect on vigilance even in the absence of suppression of melatonin secretion and that this effect can be detected when measured in subjects with low vigilance levels. Seven normal subjects were exposed to bright-white light (BL group) and seven to dim-red light (DL group) on 2 consecutive days, each following a night of 4-h sleep restriction. The light treatment was administered in the late morning, between 0900 and 1330 hours. Salivary melatonin measurements indicated that BL did not suppress melatonin secretion or induce circadian phase shifts. The effects of the two treatments were compared on validated measures of daytime vigilance: immediate effects were evaluated on subjective alertness during the light treatment, whereas short-term (0.5–10.5 h) and long-term (20.5–34.5 h) carryover effects were measured on subjective alertness, daytime sleep latencies (DSL), and psychomotor performance. After two nights of sleep restriction, subjective alertness and daytime sleep latencies decreased significantly, but there was no effect of the light treatment. BL treatment did not affect global performance, but there was an effect on the strategy used by the subjects, as shown by faster reaction times and increased percentage of errors in the BL group. It was concluded that daytime BL exposure did not have a stimulating effect on our measures of vigilance even in sleep-deprived subjects but that it may increase physiological arousal and affect the subjects’ behavior in some specific performance tasks.