Light exposure during sleep impairs cardiometabolic function

This study tested the hypothesis that acute exposure to light during nighttime sleep adversely affects next-morning glucose homeostasis and whether this effect occurs via reduced sleep quality, melatonin suppression, or sympathetic nervous system (SNS) activation during sleep. A total of 20 young adults participated in this parallel-group study design. The room light condition (n = 10) included one night of sleep in dim light (<3 lx) followed by one night of sleep with overhead room lighting (100 lx). The dim light condition (n = 10) included two consecutive nights of sleep in dim light. Measures of insulin resistance (morning homeostatic model assessment of insulin resistance, 30-min insulin area under the curve [AUC] from a 2-h oral glucose tolerance test) were higher in the room light versus dim light condition. Melatonin levels were similar in both conditions. In the room light condition, participants spent proportionately more time in stage N2 and less in slow wave and rapid eye movement sleep. Heart rate was higher and heart rate variability lower (higher sympathovagal balance) during sleep in the room light versus the dim light condition. Importantly, the higher sympathovagal balance during sleep was associated with higher 30-min insulin AUC, consistent with increased insulin resistance the following morning. These results demonstrate that a single night of exposure to room light during sleep can impair glucose homeostasis, potentially via increased SNS activation. Attention to avoiding exposure to light at night during sleep may be beneficial for cardiometabolic health.

Exposure to artificial light during the night is widespread globally, particularly in industrialized countries (1–3). Given that light and dark exposure patterns play a key role in the timing of many behaviors and physiological functions (4), exposure to light in the evening and night has been posited to be deleterious for human health and well-being (1, 5–10). Impacts of light exposure during sleep are not as well studied as other kinds of nighttime light exposure. However, a recent cross-sectional observation study noted that, compared to no light exposure during sleep, any self-reported artificial light exposure in the bedroom during sleep (small nightlight in room, light from outside room, or television/light in room) was associated with obesity in women (11). Furthermore, the incidence of obesity was highest in those who reported sleeping with a television or light on in the bedroom (11). These findings suggest that light in the bedroom during nighttime sleep may negatively influence metabolic regulation.Emerging evidence indicates that light exposure plays a role in human metabolic regulation, with evening light exposure having unfavorable effects on metabolic functions including decreased glucose tolerance and decreased insulin sensitivity (12, 13). In line with these data, we have previously shown that blue-enriched light exposure in the morning and evening alters glucose metabolism, with an increase in insulin resistance compared to dim light exposure (14). In addition, evidence indicates that nighttime indoor light exposure during the habitual sleep period while awake (15), and during sleep itself (16), likely has deleterious metabolic effects. A recent study prospectively measured light exposure in the bedroom during nighttime sleep and showed that higher levels of bedroom light exposure were associated with a higher incidence of type 2 diabetes in an elderly population (16). However, the exact mechanisms by which light exposure, particularly during nighttime sleep, impacts metabolic regulation are not well understood.A proposed pathway to explain the relationship between nighttime light exposure and altered metabolic function is via changes in sleep. Robust evidence from epidemiological and experimental studies indicates that nighttime light exposure, either from outdoor or indoor sources, has negative impacts on subjective and objective sleep quality as indicated by actigraphy or polysomnography (PSG) measures of reduced total sleep time (TST), sleep efficiency (SE), increased wake after sleep onset (WASO), reduced amount of slow wave sleep (SWS), or increased arousal index (AI) (17–20). Given the well-established contribution of sleep disruptions to metabolic dysfunction (21), it is plausible that nighttime light exposure alters glucose metabolism due to disturbances to sleep. However, nighttime light exposure also appears to have a direct effect on glucose regulation that is independent of sleep loss, as shown by a study that subjected healthy male individuals to sleep deprivation in the dark or to sleep deprivation with nighttime light exposure (22). This study showed that a full night of sleep deprivation with nighttime light exposure increased postprandial levels of insulin and glucagon-like peptide-1, increased insulin resistance, and reduced nighttime melatonin; these changes were not observed under conditions of sleep deprivation in darkness.A second proposed mechanism to explain the impairment of glucose metabolism from nighttime light exposure is via light-induced changes to the endogenous circadian system, including suppression and phase shifting of the melatonin rhythm (23). It is well established that light exposure suppresses melatonin secretion (24, 25), and several studies have implicated suppression of nighttime melatonin with incidence of diabetes (26) and insulin resistance (27). The association between altered melatonin levels and changes in glucose regulation may be explained by evidence that melatonin plays a role in the secretion and action of insulin (28–30). In particular, lower melatonin levels resulting from light exposure during the nighttime sleep period, in a fasting condition, have been suggested to alter melatonin’s facilitation of pancreatic β-cell recovery (31). Moreover, evidence shows that light exposure, even of moderate intensity, during the nighttime sleep period can produce a phase shift of the internal circadian system (32, 33). Given the established role of the circadian system in the control of glucose metabolism, light exposure during the nighttime sleep period could facilitate the misalignment between the central clock and peripheral clocks in metabolic tissues, with consequent negative impact on glucose homeostasis (34).A third potential mechanism is the effect of light exposure on autonomic nervous system (ANS) activity. Light exposure has an arousing effect on the sympathetic autonomic system as revealed by the increase in cortisol or heart rate (HR) associated with light exposure mainly during the morning and/or nighttime hours as compared to evening hours (35–37). Beyond the direct excitatory effect exerted by light exposure on sympathetic activity (35), alterations of the ANS characterized by a shift toward an increased sympathetic drive have also been suggested to mediate the negative effects of sleep disruption on many physiological systems such as glucose metabolism (38). Thus, it is plausible that light-induced autonomic activation, either directly and/or mediated by sleep disruption, significantly contributes to the observed relationship between nighttime light exposure and altered glucose metabolism. Notably, sympathetic overactivity has been shown to precede the development of insulin resistance and prediabetes and contribute to the development of obesity and metabolic syndrome (39–41).Prior studies have reported that light exposure during sleep increases HR and decreases HR variability (HRV), consistent with increased sympathetic activation (42–44). These studies either examined bright light (1,000 lx) over the entire sleep period (42) or lower light levels (50 lx or dawn simulation) early or late in the sleep period (43, 44). However, the effect of a single night of moderate room light exposure across the entire nighttime sleep period on autonomic activation and its impact on metabolic function has never been fully investigated.In the present study, we tested the hypothesis that room light exposure (100 lx) during habitual nighttime sleep is associated with increased insulin resistance as measured by the homeostatic model of insulin resistance (HOMA-IR), the Matsuda insulin sensitivity index, and impaired response to an oral glucose tolerance test (OGTT) the next morning. In addition, we hypothesized potential mechanisms of light-induced metabolic changes, such as reduced sleep quality, suppression of melatonin level, and elevated sympathetic activation (HR and HRV) during the sleep period.     

Establishing a New Research Agenda for Studying Psychiatric Emergency Room Treatment Decisions

With the growing complexity of treatment decisions made at presentation to a psychiatric emergency room (PER) and the increasing influence of managed care on the decision-making process, it is increasingly important to establish a new and more sophisticated research agenda for studying PER decision making. The main goal of this paper is to propose a comprehensive conceptual model of the PER decision-making process that will facilitate active pursuit of such a research agenda. The proposed model presents both traditional and emerging elements of the PER decision-making process (i.e., determinants, mediating mechanisms, and outcomes) and explicates the nature of the relationships among them at different levels of analysis. The model's theoretical and empirical implications for future research are discussed and suggestions are made as to the research designs and methods needed to pursue this agenda.     

Gestational pattern of heme oxygenase expression in the rat

Fetal growth is influenced by many intrinsic and extrinsic factors. Our objective was to determine the pattern of heme oxygenase (HO) expression in the pregnant rat and to study its association with fetal growth and growth factors. Uterine tissues were obtained from nonpregnant and from time-mated rats at 7, 13, 16, 19, and 21 d of pregnancy. Placental tissue was obtained on d 13, 16, 19 and 21 of pregnancy. Tissues were evaluated for HO activity, HO-1, HO-2, leptin and vascular endothelial growth factor protein, and HO-1 and HO-2 mRNA. HO activity in both the uterus and placenta peaked on d 21 of pregnancy. In the uterus, HO-1 and HO-2 protein and total mRNA levels peaked on d 16 of pregnancy, whereas, in the placenta, HO-1 and HO-2 protein levels peaked on d 19. Additionally, placental HO-1 mRNA peaked on d 16, but placental HO-2 mRNA declined toward the end of pregnancy. Placental leptin and vascular endothelial growth factor protein levels followed a similar pattern to placental HO-1 and peaked on d 16. We conclude that there is a clear uterine and placental gestational pattern of HO expression in the rat. This pattern is comparable to that of vascular endothelial growth factor and leptin.     

Interleukin-25-induced chemokines and interleukin-6 release from eosinophils is mediated by p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and nuclear factor-kappaB

Interleukin (IL)-25, a novel Th2 cytokine, is capable of amplifying allergic inflammation. We investigated the modulation of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPK) pathways in IL-25-activated eosinophils, the principal effector cells of allergic inflammation, for the in vitro release of chemokines including monocyte chemoattractant protein-1 (MCP-1), IL-8, and macrophage inflammatory protein (MIP)-1alpha, and inflammatory cytokine IL-6. Gene expression of chemokines and IL-6 was evaluated by RT-PCR, and concentrations of chemokines and cytokine were measured by cytokine protein array, cytometric bead array, and enzyme-linked immunosorbent assay. NF-kappaB, c-Jun amino-terminal kinase (JNK), and p38 MAPK activities in eosinophils were assessed by electrophoretic mobility shift assay and Western blot. IL-25 was found to upregulate the gene expression of chemokines MCP-1, MIP-1alpha, and IL-8, and cytokine IL-6, in eosinophils, and to significantly increase the release of the above chemokines and IL-6 from eosinophils. IL-25 could also activate the JNK, p38 MAPK, and NF-kappaB activities of eosinophils, while inhibitor of IkappaB-alpha phosphorylation (BAY11-7082), JNK (SP600125), and p38 MAPK (SB203580) could suppress the release of IL-8, MIP-1alpha, MCP-1, and IL-6. Together, the above results showed that the induction of MCP-1, MIP-1alpha, IL-8, and IL-6 in IL-25-activated eosinophils are regulated by JNK, p38 MAPK, and NF-kappaB pathways.     

Epstein-Barr viral load as a marker of lymphoma in AIDS patients

Epstein-Barr virus (EBV) is implicated in the pathogenesis of acquired immunodeficiency syndrome (AIDS) lymphoma, and viral DNA is present within the malignant cells in about half of affected patients. We examined the extent to which EBV viral load is elevated in the plasma of AIDS lymphoma patients compared to AIDS patients with opportunistic infections. Sixty-one AIDS patients were studied including 35 with lymphoma (24 non-Hodgkin, six Hodgkin, and five brain lymphoma) and 26 with various opportunistic infections. In situ hybridization revealed EBV encoded RNA (EBER) expression in the malignant cells of 17/28 AIDS lymphomas (61%). In 232 serial plasma samples from 35 lymphoma patients and in 128 samples from AIDS controls, EBV viral load was assayed by quantitative-polymerase chain reaction (Q-PCR) using a TaqMan probe targeting the BamH1W sequence. EBV was detected in plasma from all 17 EBER-positive AIDS lymphoma patients, with viral loads ranging from 34 to 1,500,000 copies per ml (median 3,210). Viral load usually fell rapidly upon initiation of lymphoma therapy and remained undetectable except in two patients with persistent tumor. In 11 AIDS patients, whose lymphoma lacked EBER expression, and in 26 control patients without lymphoma, levels of EBV in plasma were usually low or undetectable (range 0-1,995 and 0-2,409, median 0 and 0, respectively). There was no association between EBV viral load and human immunodeficiency virus (HIV) load or CD4 count. In conclusion, EBV viral load shows promise as a tool to assist in diagnosis and management of EBV-related lymphoma patients.     

Contribution of the forebrain archistriatal gaze fields to auditory orienting behavior in the barn owl

A region in the barn owl forebrain, referred to as the archistriatal gaze fields (AGF), is shown to be involved in auditory orienting behavior. In a previous study, electrical microstimulation of the AGF was shown to produce saccadic movements of the eyes and head, and anatomical data revealed that neurons in the AGF region of the archistriatum project directly to brainstem tegmental nuclei that mediate gaze changes. In this study, we investigated the effects of AGF inactivation on the auditory orienting responses of trained barn owls. The AGF and/or the optic tectum (OT) were inactivated pharmacologically using the GABA_A agonist muscimol. Inactivation of the AGF alone had no effect on the probability or accuracy of orienting responses to contralateral acoustic stimuli. Inactivation of the OT alone decreased the probability of responses to contralateral stimuli, but the animals were still capable of orienting accurately toward stimuli on about 60% of the trials. Inactivation of both the AGF and the OT drastically decreased the probability of responses to 16–21% and, on the few trials that the animals did respond, there was no relationship between the final direction of gaze and the location of the stimulus. Thus, with the AGF and OT both inactivated, the animals were no longer capable of orienting accurately toward acoustic stimuli located on the contralateral side. These data confirm that the AGF is involved in gaze control and that the AGF and the OT have parallel access to gaze control circuitry in the brainstem tegmentum. In these respects, the AGF in barn owls is functionally equivalent to the frontal eye fields in primates.