The aims of this study were to 1) compare the inflammatory potential of night- and day-shift nurses’ diets in regard to time-of-day and work status, and 2) explore how the timing of food intake during work and off-work is associated with cardiometabolic syndrome (CMS) risk factors between these two groups. Female nurses (N = 17; 8 day-shift and 9 night-shift) reported food intake over 9 days. On a middle day off of work, metabolic parameters were measured after an overnight fast. Energy/macronutrient intake and inflammatory potential of dietary intake (as assessed via the Dietary Inflammatory IndexTM) were calculated for nurses’ workdays, work nights, off-work days, and off-work nights. Work-night total food intake (grams) accounted for a significant amount of variance in CMS risk factors for night-shift nurses only. Increased total gram consumption during night-shift nurses’ work nights was associated with increased lipid levels – independent of the macronutrient composition of the food consumed. Alternatively, for night-shift nurses, work-day intake of several food parameters accounted for a significant proportion of variance in HDL cholesterol levels, with higher intake associated with higher HDL levels. For both day- and night-shift nurses, food intake during the day was more pro-inflammatory regardless of shift-type or work status. Our novel approach of combining time-of-day-specific and work-day-specific analyses of dietary inflammatory factors and macronutrient composition with measurement of CMS risk factors suggests a link between meal timing and cardiometabolic health for shift-working nurses.
Circadian rhythms greatly influence 24-h variation in cognition in nearly all organisms, including humans. Circadian clock impairment and sleep disruption are detrimental to hippocampusdependent memory and negatively influence the acquisition and recall of learned behaviors. The circadian clock can become out of sync with the environment during circadian misalignment. Shift work represents a real-world model of circadian misalignment that can be studied for its physiological implications. The present study aimed to test the hypothesis that circadian misalignment disrupts vigilance and cognitive performance on occupationally relevant tasks using shift work as a model. As such, we sought to 1) explore the general effects of night-and day-shift worker schedules on sleep-wake parameters and core body temperature (CBT) phase, and 2) determine whether shift-type and CBT phase impact cognitive performance and vigilance at the end of a 12-hour shift. We observed a sample of day-shift and night-shift hospital nurses over a 10day period. At the end of three, consecutive, 12-hour shifts (7pm-7am or 7am-7pm), participants completed a cognitive battery assessing vigilance, cognitive throughput, and medication calculation fluency (via an investigator developed and tested metric). Night-shift nurses exhibited significantly greater sleep fragmentation as well as a greater disparity between their wake-time and time of CBT minimum compared to day-shift nurses. Night-shift nurses exhibited significantly slower cognitive proficiency at the end of their shifts, even after adjustment for CBT phase. These results suggest that circadian disruption and reduced sleep quality both contribute to cognitive functioning and performance.
Objectives: To determine the off-shift sleep strategies of bi-ethnic night-shift nurses, the relationship between these sleep strategies and adaptation to shift work, and identify the participant-level characteristics associated with a given sleep strategy.Methods: African-American and non-Hispanic White female, night-shift nurses from an academic hospital were recruited to complete a survey on sleep–wake patterns (n = 213). Participants completed the standard shiftwork index and the biological clocks questionnaire to determine sleep strategies and adaptation to night-shift work. In addition, chronotype was determined quantitatively with a modified version of the Munich ChronoType Questionnaire. Most participants worked ~3 consecutive 12-h night-shifts followed by several days off.Results: Five sleep strategies used on days off were identified: (a) night stay, (b) nap proxy, (c) switch sleeper, (d) no sleep, and (e) incomplete switcher. Nap proxy and no sleep types were associated with poorer adaptation to night-shift work. The switch sleeper and incomplete switcher types were identified as more adaptive strategies that were associated with less sleep disturbance, a later chronotype, and less cardiovascular problems.Conclusion: Behavioral sleep strategies are related to adaptation to a typical night-shift schedule among hospital nurses. Nurses are crucial to the safety and well-being of their patients. Therefore, adoption of more adaptive sleep strategies may reduce sleep/wake dysregulation in this population, and improve cardiovascular outcomes.
Melatonin supplementation has been used as a therapeutic agent for several diseases, yet little is known about the underlying mechanisms by which melatonin synchronizes circadian rhythms. G-protein signaling plays a large role in melatonin-induced phase shifts of locomotor behavior and melatonin receptors activate G-protein-coupled inwardly rectifying potassium (GIRK) channels in Xenopus oocytes. The present study tested the hypothesis that melatonin influences circadian phase and electrical activity within the central clock in the suprachiasmatic nucleus (SCN) through GIRK channel activation. Unlike wild-type littermates, GIRK2 knock-out (KO) mice failed to phase advance wheel-running behavior in response to 3 d subcutaneous injections of melatonin in the late day. Moreover, in vitro phase resetting of the SCN circadian clock by melatonin was blocked by coadministration of a GIRK channel antagonist tertiapin-q (TPQ). Loose-patch electrophysiological recordings of SCN neurons revealed a significant reduction in the average action potential rate in response to melatonin. This effect was lost in SCN slices treated with TPQ and SCN slices from GIRK2 KO mice. The melatonin-induced suppression of firing rate corresponded with an increased inward current that was blocked by TPQ. Finally, application of ramelteon, a potent melatonin receptor agonist, significantly decreased firing rate and increased inward current within SCN neurons in a GIRKdependent manner. These results are the first to show that GIRK channels are necessary for the effects of melatonin and ramelteon within the SCN. This study suggests that GIRK channels may be an alternative therapeutic target for diseases with evidence of circadian disruption, including aberrant melatonin signaling.
Objective: Insomnia identity refers to the conviction that one has insomnia, which can occur independently of poor sleep. Night-to-night variability in sleep (termed intraindividual variability (IIV)) may contribute to insomnia identity yet remain undetected via conventional mean analyses. This study compared sleep IIV across four subgroups: noncomplaining good sleepers (NG), complaining poor sleepers (CP), complaining good sleepers (CG), and noncomplaining poor sleepers (NP). Methods: This study analyzed 14 days of sleep diary data from 723 adults. Participants were classified according to presence/absence of a sleep complaint and presence/absence of poor sleep. A 2×2 multivariate analysis of covariance (MANCOVA) was performed to explore differences on five measures of sleep IIV: intraindividual standard deviation in total sleep time (iSD TST), sleep onset latency (iSD SOL), wake after sleep onset (iSD WASO), number of nightly awakenings (iSD NWAK), and sleep efficiency (iSD SE). Results: MANCOVA revealed significant main effects of poor sleep, sleep complaint, and their interaction on sleep IIV. Poor sleepers exhibited greater IIV across all sleep parameters compared to good sleepers. Similarly, individuals with a sleep complaint exhibited greater IIV compared to individuals with no complaint. The interaction revealed that iSD SOL was significantly greater among CP than NP, and iSD NWAK was significantly greater among CG than NG. Conclusions: Greater night-to-night variability in specific sleep parameters was present among complaining versus noncomplaining sleepers in good and poor sleep subgroups. These findings suggest certain aspects of sleep consistency may be salient for treatment-seeking individuals based on their quantitative sleep status.
Key pointsr Many time-of-day cues are mediated by G protein-coupled signals within the clock centre (the suprachiasmatic nucleus, SCN) of the mammalian brain.r The role of G protein-coupled inwardly rectifying potassium (GIRK) channels in SCN function and entrainment has yet to be determined.r GIRK channels are necessary for proper day-time SCN neuronal resting membrane potential, neuropeptide Y signalling, and re-entrainment to phase advances of the light-dark (LD) cycle.r GIRK channel activation is sufficient to mimic non-photic phase shifts of the molecular clock. r GIRK channels act as an essential part of the non-photic entrainment system, and could play a critical role in diseases such as epilepsy or addiction that have strong circadian comorbidities.Abstract G protein signalling within the central circadian oscillator, the suprachiasmatic nucleus (SCN), is essential for conveying time-of-day information. We sought to determine whether G protein-coupled inwardly rectifying potassium channels (GIRKs) modulate SCN physiology and circadian behaviour. We show that GIRK current and GIRK2 protein expression are greater during the day. Pharmacological inhibition of GIRKs and genetic loss of GIRK2 depolarized the day-time resting membrane potential of SCN neurons compared to controls. Behaviourally, GIRK2 knockout (KO) mice failed to shorten free running period in response to wheel access in constant darkness and entrained more rapidly to a 6 h advance of a 12 h:12 h light-dark (LD) cycle than wild-type (WT) littermate controls. We next examined whether these effects were due to disrupted signalling of neuropeptide Y (NPY), which is known to mediate non-photic phase shifts, attenuate photic phase shifts and activate GIRKs. Indeed, GIRK2 KO SCN slices had significantly fewer silent cells in response to NPY, likely contributing to the absence of NPY-induced phase advances of PER2::LUC rhythms in organotypic SCN cultures from GIRK2 KO mice. Finally, GIRK channel activation is sufficient to cause a non-photic-like phase advance of PER2::LUC rhythms on a Per2 Luc +/− background. These results suggest that rhythmic regulation of GIRK2 protein and channel function in the SCN contributes to day-time resting membrane potential, providing a mechanism for the fine tuning responses to non-photic and photic stimuli. Further investigation could provide insight into disorders with circadian disruption comorbidities such as epilepsy and addiction, in which GIRK channels have been implicated.
The use of polypharmacy has become significantly more common over the past two decades, increasing the risk of drug-drug interactions and adverse drug reactions. Pharmacogenomic (PGx) assays have the purported benefit of being able to predict an individual's response to a specific medication based on genetic markers, which may facilitate the development of optimized medication regimens for patients prescribed polypharmacy. This 12-week pilot study examined the impact of the PGx results on the clinical management of Veterans who were prescribed psychiatric polypharmacy. Psychiatric medication providers were given access to the PGx assay results, including notification of drug-drug-gene interactions computed from an algorithm decision tool, to assist with medication management decisions. Veteran outpatients (N = 53) prescribed polypharmacy (mean = 13.15 medications) were enrolled into the study. In 92.4% of cases, providers changed medications at baseline, with 83% of providers indicating that they changed their original medication plan based on the PGx results. Clinical improvement over the 12-week treatment phase was seen in depression (F(1.63, 45) = 5.45, P = .01, η 2 = .11) and mental health quality of life (F(2.00, 45) = 4.16, P < .05, η 2 = .16). Adverse drug effects were unchanged or improved over time. Rates of polypharmacy remained unchanged. The results suggest that medication changes based on the PGx assay may be beneficial in a complex patient population prescribed polypharmacy.
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