This article reviews the current evidence associating gut microbiota with factors that impact host circadian-metabolic axis, such as light/dark cycles, sleep/wake cycles, diet, and eating patterns. We examine how gut bacteria possess their own daily rhythmicity in terms of composition, their localization to intestinal niches, and functions. We review evidence that gut bacteria modulate host rhythms via microbial metabolites such as butyrate, polyphenolic derivatives, vitamins, and amines. Lifestyle stressors such as altered sleep and eating patterns that may disturb the host circadian system also influence the gut microbiome. The consequent disruptions to microbiota-mediated functions such as decreased conjugation of bile acids or increased production of hydrogen sulfide and the resultant decreased production of butyrate, in turn affect substrate oxidation and energy regulation in the host. Thus, disturbances in microbiome rhythms may at least partially contribute to an increased risk of obesity and metabolic syndrome associated with insufficient sleep and circadian misalignment. Good sleep and a healthy diet appear to be essential for maintaining gut microbial balance. Manipulating daily rhythms of gut microbial abundance and activity may therefore hold promise for a chrononutrition-based approach to consolidate host circadian rhythms and metabolic homeorhesis.

Following general anesthesia, people are often confused about the time of day and experience sleep disruption and fatigue. It has been hypothesized that these symptoms may be caused by general anesthesia affecting the circadian clock. The circadian clock is fundamental to our well-being because it regulates almost all aspects of our daily biochemistry, physiology, and behavior. Here, we investigated the effects of the most common general anesthetic, isoflurane, on time perception and the circadian clock using the honeybee (Apis mellifera) as a model. A 6-h daytime anesthetic systematically altered the time-compensated sun compass orientation of the bees, with a mean anticlockwise shift in vanishing bearing of 87°in the Southern Hemisphere and a clockwise shift in flight direction of 58°in the Northern Hemisphere. Using the same 6-h anesthetic treatment, time-trained bees showed a delay in the start of foraging of 3.3 h, and whole-hive locomotor-activity rhythms were delayed by an average of 4.3 h. We show that these effects are all attributable to a phase delay in the core molecular clockwork. mRNA oscillations of the central clock genes cryptochrome-m and period were delayed by 4.9 and 4.3 h, respectively. However, this effect is dependent on the time of day of administration, as is common for clock effects, and nighttime anesthesia did not shift the clock. Taken together, our results suggest that general anesthesia during the day causes a persistent and marked shift of the clock effectively inducing "jet lag" and causing impaired time perception. Managing this effect in humans is likely to help expedite postoperative recovery.chronobiology | anesthesiology | post-operative sleep disruption E ver since "Ether Day" in 1846, when William Morton administered the first general anesthetic, anesthesia has been used to alleviate pain and enable a wide range of surgical procedures that were not previously possible. Today, an estimated 234 million operations requiring anesthesia occur around the world each year (1). Despite the ubiquity and importance of general anesthesia, the mechanisms by which anesthetics work to "put you to sleep" remain unclear. Recent evidence suggests that most general anesthetics act, at least in part, on the same brain centers as those involved in the control of sleep (2) and that they may "hijack" endogenous GABA-ergic (γ-aminobutyric acid) sleep-controlling pathways to exert their effects on consciousness (3). The effect of anesthesia on brain activity parallels some of the features of sleep (3). However, there are obvious differences. For example, a common patient response on emerging from anesthesia is disorientation and the feeling that time has not passed. This is in stark contrast to sleep, where one often wakes up just before the alarm sounds aware that time has passed during the night.Daily sleep timing relies on the endogenous circadian clock, which drives daily rhythms in biochemistry, physiology, and behavior. In animals, this clock is controlled by a set of conserved and well-char...

Mammals navigate by means of a metric cognitive map. Insects, most notably bees and ants, are also impressive navigators. The question whether they, too, have a metric cognitive map is important to cognitive science and neuroscience. Experimentally captured and displaced bees often depart from the release site in the compass direction they were bent on before their capture, even though this no longer heads them toward their goal. When they discover their error, however, the bees set off more or less directly toward their goal. This ability to orient toward a goal from an arbitrary point in the familiar environment is evidence that they have an integrated metric map of the experienced environment. We report a test of an alternative hypothesis, which is that all the bees have in memory is a collection of snapshots that enable them to recognize different landmarks and, associated with each such snapshot, a sun-compass-referenced home vector derived from dead reckoning done before and after previous visits to the landmark. We show that a large shift in the sun-compass rapidly induced by general anesthesia does not alter the accuracy or speed of the homeward-oriented flight made after the bees discover the error in their initial postrelease flight. This result rules out the sun-referenced home-vector hypothesis, further strengthening the now extensive evidence for a metric cognitive map in bees.navigation | course-setting | shortcuts | terrain map | circadian A metric cognitive map enables an animal to locate itself in space. In recent decades, accumulating behavioral and neurobiological evidence has established a broad consensus that the brains of mammals, and perhaps even all vertebrates, compute a metric cognitive map of the experienced environment on which they maintain a continuously updated representation of the animal's position (1-7). Because a metric map is far removed from the elementary sense data from which it must be computed, and because a map is a mathematical construction carried in a symbolic memory, the conclusion that the vertebrate brain computes a metric cognitive map of the environment is a strong argument for the computational theory of mind, which is a fundamental concept of cognitive science.The mammalian hippocampus and its putative homologs in nonmammalian vertebrates appear to play a central role in the requisite computations in vertebrates (3). Insofar as the brain's computational capacities are thought to derive from the structure of its circuits, this theory suggests that understanding the circuitry unique to the hippocampus and its homologs might be a key to constructing a neurobiologically anchored model of these computations. Before this line of thought is pursued further, it is important to know whether the construction of a metric cognitive map is limited to vertebrates. Invertebrates, particularly the social insects, whose brains are miniscule in comparison with the vertebrate brain and lacking in a homolog of the mammalian hippocampus, are nonetheless known to possess impressive ...

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SummaryIt is notoriously difficult to obtain evidence from clinical randomised controlled trials for safety innovations in healthcare. We have developed a research design using simulation for the evaluation of safety initiatives in anaesthesia. We used a standard and a modified scenario in a human-patient simulator, involving a potentially life-threatening problem requiring prompt attention -either a cardiac arrest or a failure in oxygen supply. The modified scenarios involved distractions such as loud music, a demanding and uncooperative surgeon, telephone calls and frequent questions from a medical student. Twenty anaesthetics were administered by 10 anaesthetists. A mean (SD) of 11.3 (2.8) errors per anaesthetic were identified in the oxygen failure scenarios, compared with 8.0 (3.4) in the cardiac arrest scenarios (ANOVA: p = 0.04). The difference between the combined standard scenarios and the combined modified scenarios was not significant. The mean rate of errors overall was 9.7 per simulation, with a pooled SD of 4.46, so in future studies 21 subjects would provide 80% statistical power to show a reduction in error rate of 30% from baseline with p £ 0.05. Our research design will facilitate the evaluation of safety initiatives in anaesthesia.

We implemented the World Health Organization surgical safety checklist at Auckland City Hospital from November 2007. We hypothesised that the checklist would reduce postoperative mortality and increase days alive and out of hospital, both measured to 90 postoperative days. We compared outcomes for cohorts who had surgery during 18-month periods before vs. after checklist implementation. We also analysed outcomes during 9 years that included these periods (July 2004-December 2013). We analysed 9475 patients in the 18month period before the checklist and 10,589 afterwards. We analysed 57,577 patients who had surgery from 2004 to 2013. Mean number of days alive and out of hospital (95%CI) in the cohort after checklist implementation was 1.0 (0.4-1.6) days longer than in the cohort preceding implementation, p < 0.001. Ninetyday mortality was 395/9475 (4%) and 362/10,589 (3%) in the cohorts before and after checklist implementation, multivariable odds ratio (95%CI) 0.93 (0.80-1.09), p = 0.4. The cohort changes in these outcomes were indistinguishable from longer-term trends in mortality and days alive and out of hospital observed during 9 years, as determined by Bayesian changepoint analysis. Postoperative mortality to 90 days was 228/5686 (4.0%) for M aori and 2047/51,921 (3.9%) for non-M aori, multivariable odds ratio (95%CI) 0.85 (0.73-0.99), p = 0.04. M aori spent on average (95%CI) 1.1 (0.5-1.7) fewer days alive and out of hospital than non-M aori, p < 0.001. In conclusion, our patients experienced improving postoperative outcomes from 2004 to 2013, including the periods before and after implementation of the surgical checklist. M aori patients had worse outcomes than non-M aori.

Study ObjectivesTo determine the prevalence of self-reported circadian-related sleep disorders, sleep medication and melatonin use in the New Zealand blind population.DesignA telephone survey incorporating 62 questions on sleep habits and medication together with validated questionnaires on sleep quality, chronotype and seasonality.ParticipantsParticipants were grouped into: (i) 157 with reduced conscious perception of light (RLP); (ii) 156 visually impaired with no reduction in light perception (LP) matched for age, sex and socioeconomic status, and (iii) 156 matched fully-sighted controls (FS).Sleep Habits and DisturbancesThe incidence of sleep disorders, daytime somnolence, insomnia and sleep timing problems was significantly higher in RLP and LP compared to the FS controls (p<0.001). The RLP group had the highest incidence (55%) of sleep timing problems, and 26% showed drifting sleep patterns (vs. 4% FS). Odds ratios for unconventional sleep timing were 2.41 (RLP) and 1.63 (LP) compared to FS controls. For drifting sleep patterns, they were 7.3 (RLP) and 6.0 (LP).Medication UseZopiclone was the most frequently prescribed sleep medication. Melatonin was used by only 4% in the RLP group and 2% in the LP group.ConclusionsExtrapolations from the current study suggest that 3,000 blind and visually impaired New Zealanders may suffer from circadian-related sleep problems, and that of these, fewer than 15% have been prescribed melatonin. This may represent a therapeutic gap in the treatment of circadian-related sleep disorders in New Zealand, findings that may generalize to other countries.

Elongated landscape features like forest edges, rivers, roads or boundaries of fields are particularly salient landmarks for navigating animals. Here, we ask how honeybees learn such structures and how they are used during their homing flights after being released at an unexpected location (catch-and-release paradigm). The experiments were performed in two landscapes that differed with respect to their overall structure: a rather feature-less landscape, and one rich in close and far distant landmarks. We tested three different forms of learning: learning during orientation flights, learning during training to a feeding site, and learning during homing flights after release at an unexpected site within the explored area. We found that bees use elongated ground structures, e.g., a field boundary separating two pastures close to the hive (Experiment 1), an irrigation channel (Experiment 2), a hedgerow along which the bees were trained (Experiment 3), a gravel road close to the hive and the feeder (Experiment 4), a path along an irrigation channel with its vegetation close to the feeder (Experiment 5) and a gravel road along which bees performed their homing flights (Experiment 6). Discrimination and generalization between the learned linear landmarks and similar ones in the test area depend on their object properties (irrigation channel, gravel road, hedgerow) and their compass orientation. We conclude that elongated ground structures are embedded into multiple landscape features indicating that memory of these linear structures is one component of bee navigation. Elongated structures interact and compete with other references. Object identification is an important part of this process. The objects are characterized not only by their appearance but also by their alignment in the compass. Their salience is highest if both components are close to what had been learned. High similarity in appearance can compensate for (partial) compass misalignment, and vice versa.