The effects of spectral tuning of evening ambient light on melatonin suppression, alertness and sleep

We compared the effects of bedroom-intensity light from a standard fluorescent and a blue- (i.e., short-wavelength) depleted LED source on melatonin suppression, alertness, and sleep. Sixteen healthy participants (8 females) completed a 4-day inpatient study. Participants were exposed to blue-depleted circadian-sensitive (C-LED) light and a standard fluorescent light (FL, 4100 K) of equal illuminance (50 lx) for 8 h prior to a fixed bedtime on two separate days in a within-subject, randomized, cross-over design. Each light exposure day was preceded by a dim light (< 3 lx) control at the same time 24 h earlier. Compared to the FL condition, control-adjusted melatonin suppression was significantly reduced. Although subjective sleepiness was not different between the two light conditions, auditory reaction times were significantly slower under C-LED conditions compared to FL 30 min prior to bedtime. EEG-based correlates of alertness corroborated the reduced alertness under C-LED conditions as shown by significantly increased EEG spectral power in the delta-theta (0.5�8.0 Hz) bands under C-LED as compared to FL exposure. There was no significant difference in total sleep time (TST), sleep efficiency (SE%), and slow-wave activity (SWA) between the two conditions. Unlike melatonin suppression and alertness, a significant order effect was observed on all three sleep variables, however. Individuals who received C-LED first and then FL had increased TST, SE% and SWA averaged across both nights compared to individuals who received FL first and then C-LED. These data show that the spectral characteristics of light can be fine-tuned to attenuate non-visual responses to light in humans. © 2017 Elsevier Inc

Modeling neurocognitive decline and recovery during repeated cycles of extended sleep and chronic sleep deficiency

Study Objectives: Intraindividual night-to-night sleep duration is often insufficient and variable. Here we report the effects of such chronic variable sleep deficiency on neurobehavioral performance and the ability of state-of-the-art models to predict these changes. Methods: Eight healthy males (mean age ± SD: 23.9 ± 2.4 years) studied at our inpatient intensive physiologic monitoring unit completed an 11-day protocol with a baseline 10-hour sleep opportunity and three cycles of two 3-hour time-in-bed (TIB) and one 10-hour TIB sleep opportunities. Participants received one of three polychromatic white light interventions (200 lux 4100K, 200 or 400 lux 17000K) for 3.5 hours on the morning following the second 3-hour TIB opportunity each cycle. Neurocognitive performance was assessed using the psychomotor vigilance test (PVT) administered every 1-2 hours. PVT data were compared to predictions of five group-average mathematical models that incorporate chronic sleep loss functions. Results: While PVT performance deteriorated cumulatively following each cycle of two 3-hour sleep opportunities, and improved following each 10-hour sleep opportunity, performance declined cumulatively throughout the protocol at a more accelerated rate than predicted by state-of-the-art group-average mathematical models. Subjective sleepiness did not reflect performance. The light interventions had minimal effect. Conclusions: Despite apparent recovery following each extended sleep opportunity, residual performance impairment remained and deteriorated rapidly when rechallenged with subsequent sleep loss. None of the group-average models were capable of predicting both the build-up in impairment and recovery profile of performance observed at the group or individual level, raising concerns regarding their use in real-world settings to predict performance and improve safety

Brief (<4 hr) sleep episodes are insufficient for restoring performance in first-year resident physicians working overnight extended-duration work shifts

Study Objectives: The Accreditation Council for Graduate Medical Education (ACGME) recently reinstated extended-duration (24-28 hr) work shifts (EDWS) for postgraduate year 1 (PGY-1) resident physicians. This study examined the relationship between overnight sleep duration during EDWS and subsequent �post-call� performance in PGY-1 resident physicians. Methods: Thirty-four PGY-1 resident physicians (23 males; 24-32 years) were studied between 2002 and 2004 during 3-week Q3 �on-call� rotation schedules in the Medical and Cardiac Intensive Care Units at Brigham and Women's Hospital in Boston. Daily sleep logs (validated by ambulatory polysomnography) were collected and the 10 min psychomotor vigilance task (PVT) was administered every ~6 hr during each EDWS. Generalized estimating equations were used to examine the relationship between overnight sleep duration and PVT performance �post-call� (0500-1900 hr). Postcall performance during EDWS was compared with sessions matched for time-of-day and weeks-into-schedule in the same resident physician during an intervention schedule that eliminated EDWS. Results: Resident physicians obtained an average of 1.6 ± 1.5 hr cumulative sleep overnight during EDWS (4 hr sleep (p = 0.027 versus no sleep). Despite this apparent improvement, the odds of incurring >1 attentional failure were 2.72 times higher during postcall following >4 hr sleep compared with matched sessions during non-EDWS. Conclusions: Even with >4 hr sleep overnight (8% of EDWS), performance remained significantly impaired. These findings suggest that even �strategic napping,� a recommendation recently removed from ACGME guidelines, is insufficient to mitigate severe performance impairment introduced by extending duty beyond 16 hr. © Sleep Research Society 2019. Published by Oxford University Press [on behalf of the Sleep Research Society]

Using a Single Daytime Performance Test to Identify Most Individuals at High-Risk for Performance Impairment during Extended Wake

10.1038/s41598-019-52930-yScientific Reports911668

Solid-phase library synthesis, screening, and selection of tight-binding reduced peptide bond inhibitors of a recombinant Leishmania mexicana cysteine protease B

A one-bead−two-compound inhibitor library was synthesized by the split−mix method for the identification of inhibitors of a recombinant cysteine protease from Leishmania mexicana, CPB2.8ΔCTE. The inhibitor library was composed of octapeptides with a centrally located reduced bond introduced by reductive amination of the resin-bound amines with Fmoc amino aldehydes. The library was screened on solid phase, and less than 1% of the library contained active compounds. The inhibitors displayed great specificity in the subsites flanking the enzyme catalytic triad with Cha and Ile/Leu preferred in P2, Phe in P1, Cha and Ile/Leu in P1‘, and Ile/Leu in P2‘. Some of the inhibitors were resynthesized, and the kinetics of inhibition were determined in solution-phase assays. Most of the inhibitors had micromolar Ki values, and a few inhibited the enzyme at nanomolar concentrations. One inhibitor, DKHF(CH2NH)LLVK (Ki = 1 μM), was tested for antiparasite efficacy and shown to affect parasite survival with an IC50 of approximately 50 μΜ

Sleep patterns predictive of daytime challenging behavior in individuals with low-functioning autism

Increased severity of problematic daytime behavior has been associated with poorer sleep quality in individuals with autism spectrum disorder. In this work, we investigate whether this relationship holds in a real-time setting, such that an individual's prior sleep can be used to predict their subsequent daytime behavior. We analyzed an extensive real-world dataset containing over 20,000 nightly sleep observations matched to subsequent challenging daytime behaviors (aggression, self-injury, tantrums, property destruction and a challenging behavior index) across 67 individuals with low-functioning autism living in two U.S. residential facilities. Using support vector machine classifiers, a statistically significant predictive relationship was found in 81% of individuals studied (P < 0.05). For all five behaviors examined, prediction accuracy increased up to approximately eight nights of prior sleep used to make the prediction, indicating that the behavioral effects of sleep may manifest on extended timescales. Accurate prediction was most strongly driven by sleep variability measures, highlighting the importance of regular sleep patterns. Our findings constitute an initial step towards the development of a real-time monitoring tool to pre-empt behavioral episodes and guide prophylactic treatment for individuals with autism. Autism Res 2018, 11: 391�403. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary: We analyzed over 20,000 nights of sleep from 67 individuals with autism to investigate whether daytime behaviors can be predicted from prior sleep patterns. Better-than-chance accuracy was obtained for 81% of individuals, with measures of night-to-night variation in sleep timing and duration most relevant for accurate prediction. Our results highlight the importance of regular sleep patterns for better daytime functioning and represent a step toward the development of �smart sleep technologies' to pre-empt behavior in individuals with autism. © 2017 International Society for Autism Research, Wiley Periodicals, Inc