Effects of Exposure to Intermittent versus Continuous Red Light on Human Circadian Rhythms, Melatonin Suppression, and Pupillary Constriction

Exposure to light is a major determinant of sleep timing and hormonal rhythms. The role of retinal cones in regulating circadian physiology remains unclear, however, as most studies have used light exposures that also activate the photopigment melanopsin. Here, we tested the hypothesis that exposure to alternating red light and darkness can enhance circadian resetting responses in humans by repeatedly activating cone photoreceptors. In a between-subjects study, healthy volunteers (n = 24, 21–28 yr) lived individually in a laboratory for 6 consecutive days. Circadian rhythms of melatonin, cortisol, body temperature, and heart rate were assessed before and after exposure to 6 h of continuous red light (631 nm, 13 log photons cm−2 s−1), intermittent red light (1 min on/off), or bright white light (2,500 lux) near the onset of nocturnal melatonin secretion (n = 8 in each group). Melatonin suppression and pupillary constriction were also assessed during light exposure. We found that circadian resetting responses were similar for exposure to continuous versus intermittent red light (P = 0.69), with an average phase delay shift of almost an hour. Surprisingly, 2 subjects who were exposed to red light exhibited circadian responses similar in magnitude to those who were exposed to bright white light. Red light also elicited prolonged pupillary constriction, but did not suppress melatonin levels. These findings suggest that, for red light stimuli outside the range of sensitivity for melanopsin, cone photoreceptors can mediate circadian phase resetting of physiologic rhythms in some individuals. Our results also show that sensitivity thresholds differ across non-visual light responses, suggesting that cones may contribute differentially to circadian resetting, melatonin suppression, and the pupillary light reflex during exposure to continuous light

Nipah Virus Encephalitis Reemergence, Bangladesh

Two Nipah virus encephalitis outbreaks in Bangladesh may be associated with person-to-person transmission

Kinematics of prospective motor control in autism spectrum disorder : an exploratory multilevel modelling analysis of goal-directed finger movements during smart-tablet gameplay

Background: Disturbance in movement is widely observed in autism and differences have been measured at the level of movement kinematics. Anzulewicz et al (2016) showed that gesture patterns from smart-tablet gameplay can distinguish between children with autism (ASD) and typically developing children (TD) with high accuracy using a machine learning algorithm, but a limitation of the data-driven approach used is that distinguishing features included in the algorithm may not be grounded in theory. It has been suggested that prospective control of movement is disrupted in autism, and this may result from impairments in using sensory feedback as the movement unfolds, despite intact control of internally generated movements. Furthermore, movement kinematics variables which are influenced by task difficulty and change with motor development have been identified to indicate prospective motor control.Objectives: The objective of the analysis is to explore differences between ASD and TD children in the kinematics of prospective motor control during goal-directed finger movements to different target distances, using data collected by Anzulewicz et al (2016).Methods: Touch-screen position coordinates of 4775 goal-directed swipes made during a smart-tablet gameplay by 82 children, aged 3-5 years old, were analysed. Target distance was calculated as the length between start and end position of each swipe and five kinematic variables related to prospective motor control were calculated from time differentials of position, namely: (1) peak velocity of the full movement, (2) peak velocity of the first movement unit (1MU), (3) number of movement units (velocity peaks), (4) % time in deceleration and (5) % time to peak velocity. Multilevel modelling was used to analyse the fixed effects and interaction effect of target distance and ASD diagnosis on each kinematic outcome, including a random effect to control for correlation in the kinematic outcome for swipes by the same individual.Results: Increase in 1cm target distance led to an increase in peak velocity of the full movement, and ASD children showed a greater increase than TD (Interaction: 3%, CI: 1% to 4%, p<0.001). TD children showed a 3% reduction in peak velocity (1MU) (CI: -5% to 0%, p=0.05) and decelerate 0.41% longer (CI: 0.20% - 0.63%, p<0.001) for more distant targets, but children with ASD showed the opposite relationship (Peak velocity (1MU) - Interaction: 9%, CI: 3% to 14%, p<0.001; Deceleration - interaction: -0.54%, CI: -0.93% to -0.14%, p=0.008). ASD children reached a peak in velocity later for more distant targets (Interaction: 1.28%, CI: 0.39% to 2.16%, p=0.005), but no relationship is seen for TD children. Overall, ASD children have 31% more movement units than TD (CI: 1% to 70%, p=0.04), but a 3% smaller increase in movement units for more distant targets (CI: -5% to -1%, p=0.007).Conclusions: The kinematics of prospective control is different for children with ASD and TD, and may help to identify children with autism. These findings are consistent with the idea that individuals with ASD may differ in the use of feedback control, and internal feedforward control may be influenced differently by external constraints such as target distance

Developmental differences in the prospective organisation of goal-directed movement between children with autism and typically developing children : a smart tablet serious game study

Movement is prospective. It structures self-generated engagement with objects and social partners and is fundamental to children's learning and development. In autistic children, previous reports of differences in movement kinematics compared to neurotypical peers suggest that its prospective organisation might be disrupted. Here, we employed a smart tablet serious game paradigm to assess differences in the feedforward and feedback mechanisms of prospective action organisation, between autistic and neurotypical preschool children. We analysed 3926 goal-directed finger movements made during smart-tablet ecological gameplay, from 28 children with Childhood Autism (ICD-10; ASD) and 43 neurotypical children (TD), aged 3–6 years old. Using linear and generalised linear mixed-effect models, we found the ASD group executed movements with longer movement time (MT) and time to peak velocity (TTPV), lower peak velocity (PV), with PV less likely to occur in the first movement unit (MU) and with a greater number of movement units after peak velocity (MU-APV). Interestingly, compared to the TD group, the ASD group showed smaller increases in PV, TTPV and MT with an increase in age (ASD × age interaction), together with a smaller reduction in MU-APV and an increase in MU-APV at shorter target distances (ASD × Dist interaction). Our results are the first to highlight different developmental trends in anticipatory feedforward and compensatory feedback mechanisms of control, contributing to differences in movement kinematics observed between autistic and neurotypical children. These findings point to differences in integration of prospective perceptuomotor information, with implications for embodied cognition and learning from self-generated action in autism

HIF-Independent Regulation of Thioredoxin Reductase 1 Contributes to the High Levels of Reactive Oxygen Species Induced by Hypoxia

Cellular adaptation to hypoxic conditions mainly involves transcriptional changes in which hypoxia inducible factors (HIFs) play a critical role. Under hypoxic conditions, HIF protein is stabilized due to inhibition of the activity of prolyl hydroxylases (EGLNs). Because the reaction carried out by these enzymes uses oxygen as a co-substrate it is generally accepted that the hypoxic inhibition of EGLNs is due to the reduction in oxygen levels. However, several studies have reported that hypoxic generation of mitochondrial reactive oxygen species (ROS) is required for HIF stabilization. Here, we show that hypoxia downregulates thioredoxin reductase 1 (TR1) mRNA and protein levels. This hypoxic TR1 regulation is HIF independent, as HIF stabilization by EGLNs inhibitors does not affect TR1 expression and HIF deficiency does not block TR1 hypoxic-regulation, and it has an effect on TR1 function, as hypoxic conditions also reduce TR1 activity. We found that, when cultured under hypoxic conditions, TR1 deficient cells showed a larger accumulation of ROS compared to control cells, whereas TR1 over-expression was able to block the hypoxic generation of ROS. Furthermore, the changes in ROS levels observed in TR1 deficient or TR1 over-expressing cells did not affect HIF stabilization or function. These results indicate that hypoxic TR1 down-regulation is important in maintaining high levels of ROS under hypoxic conditions and that HIF stabilization and activity do not require hypoxic generation of ROS

An outbreak of Streptococcus pyogenes in a mental health facility : advantage of well-timed whole-genome sequencing over emm typing

Financial support: The outbreak investigation was supported by Institute of Mental Health.OBJECTIVE:  We report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing. SETTING:  A 2,000-bed tertiary-care psychiatric hospital. METHODS:  Active surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)-based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak. RESULTS:  The study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1-C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0-5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21-45 and 26-58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology. CONCLUSIONS:  WGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.PostprintPeer reviewe

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data