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Light therapy is used to treat sleep and circadian rhythm disorders, yet there are limited studies on whether light therapy impacts electroencephalographic (EEG) activity during sleep. Therefore, we aimed to provide an overview of research studies that examined the effects of light therapy on sleep macro- and micro-architecture in populations with sleep and circadian rhythm disorders. We searched for randomized controlled trials that used light therapy and included EEG sleep measures using MEDLINE, PubMed, CINAHL, PsycINFO and Cochrane Central Register of Controlled Trials databases. Five articles met the inclusion criteria of patients with either insomnia or delayed sleep–wake phase disorder (DSWPD). These trials reported sleep macro-architecture outcomes using EEG or polysomnography. Three insomnia trials showed no effect of the timing or intensity of light therapy on total sleep time, wake after sleep onset, sleep efficiency and sleep stage duration compared to controls. Only one insomnia trial reported significantly higher sleep efficiency after evening light therapy (>4000 lx between 21:00–23:00 h) compared with afternoon light therapy (>4000 lx between 15:00–17:00 h). In the only DSWPD trial, six multiple sleep latency tests were conducted across the day (09:00 and 19:00 h) and bright light (2500 lx) significantly lengthened sleep latency in the morning (09:00 and 11:00 h) compared to control light (300 lx). None of the five trials reported any sleep micro-architecture measures. Overall, there was limited research about the effect of light therapy on EEG sleep measures, and studies were confined to patients with insomnia and DSWPD only. More research is needed to better understand whether lighting interventions in clinical populations affect sleep macro- and micro-architecture and objective sleep timing and quality.

Introduction While digital health interventions (DHIs) can potentially address the unmet needs for sleep health services, little is known about their implementation in practice. The current study aimed to explore primary care health providers’ attitudes and beliefs towards DHIs for sleep and implementation into practice. Methods A cross-sectional online survey was administered to Australian primary care health professionals: general practitioners (GPs), community nurses, and community pharmacists. Semi-structured interviews were conducted within a sub-sample of participants exploring their experiences with DHIs and perceived barriers/facilitators for embedding DHIs into primary care. Semi-structured interviews were thematically analysed using the framework approach to contextualise survey findings. Results Ninety-six surveys were returned (GPs = 36, nurses = 30, and pharmacists = 30) and 45 interviews conducted (GPs = 17, nurses = 14, and pharmacists = 14). From the survey, GPs were more likely to endorse familiarity ( p = 0.009) and use ( p

Abstract Insomnia disorder (ID) is a heterogeneous disorder with proposed subtypes based on objective sleep duration. We speculated that insomnia subtyping with additional power spectral analysis and measurement of response to acute sleep restriction may be informative in overall assessment of ID. To explore alternative classifications of ID subtypes, insomnia patients (n = 99) underwent two consecutive overnight sleep studies: (i) habitual sleep opportunity (polysomnography, PSG) and, (ii) two hours less sleep opportunity (electroencephalography, EEG), with the first night compared to healthy controls (n = 25). ID subtypes were derived from data-driven classification of PSG, EEG spectral power and interhemispheric EEG asymmetry index. Three insomnia subtypes with different sleep duration and NREM spectral power were identified. One subtype (n = 26) had shorter sleep duration and lower NREM delta power than healthy controls (short-sleep delta-deficient; SSDD), the second subtype (n = 51) had normal sleep duration but lower NREM delta power than healthy controls (normal-sleep delta-deficient; NSDD) and a third subtype showed (n = 22) no difference in sleep duration or delta power from healthy controls (normal neurophysiological sleep; NNS). Acute sleep restriction improved multiple objective sleep measures across all insomnia subtypes including increased delta power in SSDD and NSDD, and improvements in subjective sleep quality for SSDD (p = 0.03), with a trend observed for NSDD (p = 0.057). These exploratory results suggest evidence of novel neurophysiological insomnia subtypes that may inform sleep state misperception in ID and with further research, may provide pathways for personalised care.

Abstract Background This systematic review aimed to investigate whether the administration of hypnotic medicines, z-drugs, melatonin or benzodiazepines, reduced pain intensity postoperatively. Methods Medline, Embase, Cinahl, Psych info, Central and PubMed databases were searched, from inception to February 2020 to identify relevant trials. The search was extended, post hoc, to include meta-Register of Controlled Trials, the Web of Science and the conference booklets for the 14th, 15th, and 16th International Association for the Study of Pain conferences. Two independent reviewers screened titles and abstracts and cross-checked the extracted data. Results The search retrieved 5546 articles. After full-text screening, 15 trials were included, which had randomised 1252 participants. There is moderate-quality evidence that in the short-term [WMD − 1.06, CI − 1.48 to − 0.64, p ≤ .01] and low-quality evidence that in the medium-term [WMD − 0.90, CI − 1.43 to − 0.37, p ≤ .01] postoperative period oral zolpidem 5/10 mg with other analgesic medicines reduced pain intensity compared to the same analgesic medicines alone. There is low-quality evidence that melatonin was not effective on postoperative pain intensity compared to placebo. The results of benzodiazepines on pain intensity were mixed. The authors reported no significant adverse events. Conclusions There is promising evidence that the hypnotic medicine zolpidem, adjuvant to other analgesics, is effective at achieving a minimally clinically important difference in pain intensity postoperatively. There is no consistent effect of melatonin or benzodiazepines on postoperative pain intensity. Readers should interpret these results with some caution due to the lack of data on safety, the small number of trials included in the pooled effects and their sample sizes. Systematic review registration The protocol for this systematic review was registered with PROSPERO ID= CRD42015025327 .

Insomnia is a highly prevalent sleep disorder with strong bidirectional associations with depressive symptoms. The circadian preference for eveningness has been shown to be associated with depressive symptoms in insomnia and other mental health conditions. However, there is a lack of studies in insomnia investigating whether objective measures, such as dim light melatonin onset (DLMO) or polysomnographic (PSG) sleep, are associated with depressive symptoms. Therefore, we investigated the associations between subjective measures (questionnaires assessing anxiety, sleep quality and circadian preference, and sleep diary) and depressive symptoms and whether the addition of objective measures (DLMO, PSG parameters) would strengthen the associations with depressive symptoms. In 115 insomnia disorder patients we found that anxiety was strongly associated with depressive symptoms in a model including circadian preference, dysfunctional beliefs of sleep, and self-reported previous depressive symptoms (R2 = 0.496, p < 0.001). The addition of sleep diary measures did not strengthen the model. We also found that the addition of objective measures (DLMO, PSG parameters) did not improve the subjective associations with depressive symptoms. Our data suggest that objective circadian markers are less important in the prediction of depressive symptoms in insomnia compared to subjective measures.

Abstract In this retrospective cohort study, we describe acceptability, tolerability and potential efficacy of cognitive behavioural therapy (CBT) in Insomnia Disorder subtypes, derived from polysomnography (PSG): insomnia with normal-sleep duration (I-NSD) and insomnia with short-sleep duration (I-SSD). All research volunteers were offered access to digital CBT, single component sleep restriction therapy and face-to-face group CBT. Follow-up occurred at three months post-treatment using the insomnia severity index (ISI). 96 participants (61 females, mean age of 41 years) were grouped into either normal-sleep (n = 53) or short-sleep (n = 43). CBT was acceptable to 63% of participants (normal-sleep = 31, short-sleep = 29), with 28 completing therapy (tolerability: normal-sleep = 11, short-sleep = 17). For potential efficacy, 39 (normal-sleep = 20, short-sleep = 19) out of 96 participants (41%) completed a follow-up ISI assessment. In this reduced sample, mean (SD) ISI scores decreased across both groups (normal-sleep: 18.0 (4.0) to 10.7 (4.6); short-sleep: 16.5 (5.5) to 11.0 (6.3); both P

Abstract Background Hand hygiene compliance is the basis of infection control programs. In developing countries models to improve hand hygiene compliance to reduce healthcare acquired infections are required. The aim of this study was to determine hand hygiene compliance following an educational program in an obstetric and gynecological hospital in Vietnam. Methods Health care workers from neonatal intensive care, delivery suite and a surgical ward from Hung Vuong Hospital, Ho Chi Minh City, Vietnam undertook a 4-h educational program targeting hand hygiene. Compliance was monitored monthly for six months following the intervention. Hand hygiene knowledge was assessed at baseline and after six months of the study. Results There were 7124 opportunities over 370 hand hygiene recording sessions with 1531 opportunities at baseline and 1620 at 6 months following the intervention. Hand hygiene compliance increased significantly from baseline across all sites (43.6% [95% Confidence interval CI: 41.1–46.1] to 63% [95% CI: 60.6–65.3]; p

Abstract Background Large scale models of interprofessional learning (IPL) where outcomes are assessed are rare within health professional curricula. To date, there is sparse research describing robust assessment strategies to support such activities. We describe the development of an IPL assessment task based on peer rating of a student generated video evidencing collaborative interprofessional practice. We provide content validation evidence of an assessment rubric in the context of large scale IPL. Methods Two established approaches to scale development in an educational setting were combined. A literature review was undertaken to develop a conceptual model of the relevant domains and issues pertaining to assessment of student generated videos within IPL. Starting with a prototype rubric developed from the literature, a series of staff and student workshops were undertaken to integrate expert opinion and user perspectives. Participants assessed five-minute videos produced in a prior pilot IPL activity. Outcomes from each workshop informed the next version of the rubric until agreement was reached on anchoring statements and criteria. At this point the rubric was declared fit to be used in the upcoming mandatory large scale IPL activity. Results The assessment rubric consisted of four domains: patient issues, interprofessional negotiation; interprofessional management plan in action; and effective use of video medium to engage audience. The first three domains reflected topic content relevant to the underlying construct of interprofessional collaborative practice. The fourth domain was consistent with the broader video assessment literature calling for greater emphasis on creativity in education. Conclusions We have provided evidence for the content validity of a video-based peer assessment task portraying interprofessional collaborative practice in the context of large-scale IPL activities for healthcare professional students. Further research is needed to establish the reliability of such a scale.

Abstract Circadian clocks regulate the daily timing of many of our physiological, metabolic and biochemical functions. The immune system also displays circadian oscillations in immune cell count, synthesis and cytokine release, clock gene expression in cells and organs of the immune system as well as clock-controlled genes that regulate immune function. Circadian disruption leads to dysregulation of immune responses and inflammation which can further disrupt circadian rhythms. The response of organisms to immune challenges, such as allergic reactions also vary depending on time of the day, which can lead to detrimental responses particularly during the rest and early active periods. This review evaluates what is currently known in terms of circadian biology of immune response and the cross-talk between circadian and immune system. We discuss the circadian pattern of three respiratory-related inflammatory diseases, chronic obstructive pulmonary disease, allergic rhinitis and asthma. Increasing our knowledge on circadian patterns of immune responses and developing chronotherapeutic studies in inflammatory diseases with strong circadian patterns will lead to preventive measures as well as improved therapies focussing on the circadian rhythms of symptoms and the daily variation of the patients’ responses to medication.

Background: Insomnia disorder is a highly prevalent health condition, affecting ~10–15% of the adult population worldwide. A central feature of insomnia is hyperarousal characterized as persistent and increased somatic, cognitive and cortical stimulation. Hyperarousal leads to a state of conditioned arousal that disrupts both sleep and daytime function. Research studies have shown increases in body temperature, heart rate, electroencephalographic activity, catecholamines, and oxygen consumption as a measure of metabolic rate. These findings provide evidence of increased physiological activation in insomnia however results are not consistent. The aim of the systematic review was to determine if metabolic rate in patients with insomnia is increased in keeping with the hyperarousal hypothesis.Methods: We searched Pubmed, Web of Science, CINAHL, PsycINFO, EMBASE, and Scopus databases for observational and interventional studies that have measured metabolic rate in insomnia. Study characteristics were extracted and summarized and a risk of bias was performed for each of the studies.Results: Two reviewers screened 963 abstracts with 35 articles of interest for full-text review. Four articles evaluating 75 participants were included in this systematic review. Two studies showed increased oxygen consumption across 24 h in insomnia patients compared with good-sleeping controls. One study which measured oxygen consumption at only a single timepoint showed no difference between insomnia patients and good-sleeping controls. A further study evaluating the effect of lorazepam on oxygen consumption in patients with chronic insomnia showed that lorazepam reduced metabolic rate during the night time only.Conclusions: These findings show that metabolic rate appears to be increased across 24 h in line with the hyperarousal model of insomnia. However, these increases in metabolic rate in insomnia were minor compared to good-sleeping controls and the clinical significance is unclear. Larger, methodologically robust studies are required to confirm these findings and the effect of any increase in metabolic rate on sleep-wake disturbances or pathophysiology.

Abstract Background The assessment of team performance within large-scale Interprofessional Learning (IPL) initiatives is an important but underexplored area. It is essential for demonstrating the effectiveness of collaborative learning outcomes in preparing students for professional practice. Using Kane’s validity framework, we investigated whether peer assessment of student-produced videos depicting collaborative teamwork in an IPL activity was sufficiently valid for decision-making about team performance, and where the sources of error might lie to optimise future iterations of the assessment. Methods A large cohort of health professional students (n = 1218) of 8 differing professions was divided into teams containing 5–6 students. Each team collaborated on producing a short video to evidence their management of one of 12 complex patient cases. Students from two other teams, who had worked on the same case, individually rated each video using a previously developed assessment scale. A generalisability study quantified sources of error that impacted the reliability of peer assessment of collaborative teamwork. A decision study modeled the impact of differing numbers of raters. A modified Angoff determined the pass/fail mark. Results Within a large-scale learning activity, peer assessment of collaborative teamwork was reliable (G = 0.71) based on scoring by students from two teams (n = 10–12) for each video. The main sources of variation were the stringency and subjectivity of fellow student assessors. Whilst professions marked with differing stringency, and individual student assessors had different views of the quality of a particular video, none of that individual assessor variance was attributable to the assessors’ profession. Teams performed similarly across the 12 cases overall, and no particular professions marked differently on any particular case. Conclusion A peer assessment of a student-produced video depicting interprofessional collaborative teamwork around the management of complex patient cases can be valid for decision-making about student team performance. Further refining marking rubrics and student assessor training could potentially modify assessor subjectivity. The impact of professions on assessing individual peers and the case-specificity of team performances in IPL settings need further exploration. This innovative approach to assessment offers a promising avenue for enhancing the measurement of collaborative learning outcomes in large-scale Interprofessional learning initiatives.

Objective Insomnia is the most prevalent sleep disorder, with few effective pharmacotherapies. Anecdotal reports and recent preclinical research suggest that cannabinol (CBN), a constituent of Cannabis sativa derived from delta-9-tetrahydrocannabinol, could be an effective treatment. Despite this, the isolated effects of CBN on sleep have yet to be systematically studied in humans.Methods The present protocol paper describes a randomised, double-blind, placebo-controlled, single-dose, three-arm, cross-over, proof-of-concept study which investigates the effects of CBN on sleep and next-day function in 20 participants with clinician-diagnosed insomnia disorder and an Insomnia Severity Index Score ≥15. Participants receive a single fixed oral liquid dose of 30 mg CBN, 300 mg CBN and matched placebo, in random order on three treatment nights; each separated by a 2-week wash-out period. Participants undergo overnight sleep assessment using in-laboratory polysomnography and next-day neurobehavioural function tests. The primary outcome is wake after sleep onset minutes. Secondary outcomes include changes to traditional sleep staging, sleep-onset latency and absolute spectral power during non-rapid eye movement (NREM) sleep. Tertiary outcomes include changes to sleep spindles during NREM sleep, arousal indices, absolute spectral power during REM sleep and subjective sleep quality. Safety-related and exploratory outcomes include changes to next-day simulated driving performance, subjective mood and drug effects, postural sway, alertness and reaction time, overnight memory consolidation, pre and post-sleep subjective and objective sleepiness; and plasma, urinary, and salivary cannabinoid concentrations. The study will provide novel preliminary data on CBN efficacy and safety in insomnia disorder, which will inform larger clinical trials.Ethics and dissemination Human Research Ethics Committee approval has been granted by Bellberry (2021-08-907). Study findings will be disseminated in a peer-reviewed journal and at academic conferences.Trial registration number NCT05344170.

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (|fold change| ≥ 1.5 and p ≤ 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4°C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice. [ABSTRACT FROM AUTHOR]

Introduction Melatonin has multiple proposed therapeutic benefits including antioxidant properties, synchronisation of the circadian system and lowering of blood pressure. In this protocol, we outline a randomised controlled trial to assess the feasibility, acceptability and tolerability of higher dose (25 mg) melatonin to target brain oxidative stress and sleep disturbance in older adults with mild cognitive impairment (MCI).Methods and analysis The study design is a randomised double-blind, placebo-controlled, parallel group trial. Forty individuals with MCI will be recruited from the Healthy Brain Ageing Clinic, University of Sydney and from the community, and randomised to receive either 25 mg oral melatonin or placebo nightly for 12 weeks. The primary outcomes are feasibility of recruitment, acceptability of intervention and adherence to trial medication at 12 weeks. Secondary outcomes will include the effect of melatonin on brain oxidative stress as measured by magnetic resonance spectroscopy, blood pressure, blood biomarkers, mood, cognition and sleep. Outcomes will be collected at 6 and 12 weeks. The results of this feasibility trial will inform a future conclusive randomised controlled trial to specifically test the efficacy of melatonin on modifiable risk factors of dementia, as well as cognition and brain function. This will be the first trial to investigate the effect of melatonin in the population with MCI in this way, with the future aim of using this approach to reduce progression to dementia.Ethics and dissemination This protocol has been approved by the Sydney Local Health District Ethics Committee (X18-0077). This randomised controlled trial will be conducted in compliance with the protocol published in the registry, the International Conference for Harmonisation on Good Clinical Practice and all other applicable regulatory requirements. The findings of the trial will be disseminated via conferences, publications and media, as applicable. Participants will be informed of results of the study at the conclusion of the trial. Eligible authors will include investigators who are involved in the conception and design of the study, the conduct of the trial, the analysis of the results, and reporting and presentation of study findings.Trial registration number Australian and New Zealand Clinical Trials Registry (ANZCTRN 12619000876190).Protocol version V.8 15 October 2020.

Introduction Insomnia is a highly prevalent and costly condition that is associated with increased health risks and healthcare utilisation. Anecdotally, cannabis use is frequently reported by consumers to promote sleep. However, there is limited research on the effects of cannabis on sleep and daytime function in people with insomnia disorder using objective measures. This proof-of-concept study will evaluate the effects of a single dose of an oral cannabis-based medicine on sleep and daytime function in participants with chronic insomnia disorder.Methods and analysis A randomised, crossover, placebo-controlled, single-dose study design will be used to test the safety and efficacy of an oral oil solution (‘ETC120’) containing 10 mg Δ9-tetrahydrocannabinol (THC) and 200 mg cannabidiol (CBD) in 20 participants diagnosed with chronic insomnia disorder. Participants aged 35–60 years will be recruited over an 18-month period commencing August 2019. Each participant will receive both the active drug and matched placebo, in a counterbalanced order, during two overnight study assessment visits, with at least a 1-week washout period between each visit. The primary outcomes are total sleep time and wake after sleep onset assessed via polysomnography. In addition, 256-channel high-density electroencephalography and source modelling using structural brain MRI will be used to comprehensively examine brain activation during sleep and wake periods on ETC120 versus placebo. Next-day cognitive function, alertness and simulated driving performance will also be investigated.Ethics and dissemination Ethics approval was received from Bellberry Human Research Ethics Committee (2018-04-284). The findings will be disseminated in a peer-reviewed open-access journal and at academic conferences.Trial registration number ANZCTRN12619000714189.

BackgroundDelayed Sleep-Wake Phase Disorder (DSWPD) is characterised by sleep initiation insomnia when attempting sleep at conventional times and difficulty waking at the required time for daytime commitments. Although there are published therapeutic guidelines for the administration of melatonin for DSWPD, to our knowledge, randomised controlled trials are lacking. This trial tested the efficacy of 0.5 mg melatonin, combined with behavioural sleep-wake scheduling, for improving sleep initiation in clinically diagnosed DSWPD patients with a delayed endogenous melatonin rhythm relative to patient-desired (or -required) bedtime (DBT).MethodsThis randomised, placebo-controlled, double-blind clinical trial was conducted in an Australian outpatient DSWPD population. Following 1-wk baseline, clinically diagnosed DSWPD patients with delayed melatonin rhythm relative to DBT (salivary dim light melatonin onset [DLMO] after or within 30 min before DBT) were randomised to 4-wk treatment with 0.5 mg fast-release melatonin or placebo 1 h before DBT for at least 5 consecutive nights per week. All patients received behavioural sleep-wake scheduling, consisting of bedtime scheduled at DBT. The primary outcome was actigraphic sleep onset time. Secondary outcomes were sleep efficiency in the first third of time in bed (SE T1) on treatment nights, subjective sleep-related daytime impairment (Patient Reported Outcomes Measurement Information System [PROMIS]), PROMIS sleep disturbance, measures of daytime sleepiness, clinician-rated change in illness severity, and DLMO time.FindingsBetween September 13, 2012 and September 1, 2014, 307 participants were registered; 116 were randomised to treatment (intention-to-treat n = 116; n = 62 males; mean age, 29.0 y). Relative to baseline and compared to placebo, sleep onset occurred 34 min earlier (95% confidence interval [CI] -60 to -8) in the melatonin group. SE T1 increased; PROMIS sleep-related impairment, PROMIS sleep disturbance, insomnia severity, and functional disability decreased; and a greater proportion of patients showed more than minimal clinician-rated improvement following melatonin treatment (52.8%) compared to placebo (24.0%) (P < 0.05). The groups did not differ in the number of nights treatment was taken per protocol. Post-treatment DLMO assessed in a subset of patients (n = 43) was not significantly different between groups. Adverse events included light-headedness, daytime sleepiness, and decreased libido, although rates were similar between treatment groups. The clinical benefits or safety of melatonin with long-term treatment were not assessed, and it remains unknown whether the same treatment regime would benefit patients experiencing DSWPD sleep symptomology without a delay in the endogenous melatonin rhythm.ConclusionsIn this study, melatonin treatment 1 h prior to DBT combined with behavioural sleep-wake scheduling was efficacious for improving objective and subjective measures of sleep disturbances and sleep-related impairments in DSWPD patients with delayed circadian phase relative to DBT. Improvements were achieved largely through the sleep-promoting effects of melatonin, combined with behavioural sleep-wake scheduling.Trial registrationThis trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000425897.

OBJECTIVES:The aim of this preliminary study was to evaluate if Sleep Restriction Therapy for insomnia is associated with modifications to physiological arousal, indexed through overnight measures of plasma cortisol concentrations and core body temperature. METHODS:In a pre-to-post open label study design, eleven patients with chronic and severe Psychophysiological Insomnia underwent 5 weeks of Sleep Restriction Therapy. RESULTS:Eight (73%) patients out of 11 consented completed therapy and showed a decrease in insomnia severity pre-to-post treatment (mean (SD): 18.1 (2.8) versus 8.4 (4.8); p = .001). Six patients were analyzed with pre-to-post overnight measures of temperature and cortisol. Contrary to our hypothesis, significantly higher levels of plasma cortisol concentrations were found during the early morning at post-treatment compared to baseline (p < .01), while no change was observed in the pre-sleep phase or early part of the night. Core body temperature during sleep was however reduced significantly (overall mean [95% CI]: 36.54 (°C) [36.3, 36.8] versus 36.45 [36.2, 36.7]; p < .05). CONCLUSIONS:Sleep Restriction Therapy therefore was associated with increased early morning cortisol concentrations and decreased core body temperature, supporting the premise of physiological changes in functioning after effective therapy. Future work should evaluate change in physiological variables associated with clinical treatment response. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry ANZCTR 12612000049875.

Mice are housed at temperatures (20-26 °C) that increase their basal metabolic rates and impose high energy demands to maintain core temperatures. Therefore, energy must be reallocated from other biological processes to increase heat production to offset heat loss. Supplying laboratory mice with nesting material may provide sufficient insulation to reduce heat loss and improve both feed conversion and breeding performance. Naïve C57BL/6, BALB/c, and CD-1 breeding pairs were provided with bedding alone, or bedding supplemented with either 8 g of Enviro-Dri, 8 g of Nestlets, for 6 months. Mice provided with either nesting material built more dome-like nests than controls. Nesting material improved feed efficiency per pup weaned as well as pup weaning weight. The breeding index (pups weaned/dam/week) was higher when either nesting material was provided. Thus, the sparing of energy for thermoregulation of mice given additional nesting material may have been responsible for the improved breeding and growth of offspring.

In laboratories, mice are housed at 20-24°C, which is below their lower critical temperature (≈30°C). This increased thermal stress has the potential to alter scientific outcomes. Nesting material should allow for improved behavioral thermoregulation and thus alleviate this thermal stress. Nesting behavior should change with temperature and material, and the choice between nesting or thermotaxis (movement in response to temperature) should also depend on the balance of these factors, such that mice titrate nesting material against temperature. Naïve CD-1, BALB/c, and C57BL/6 mice (36 male and 36 female/strain in groups of 3) were housed in a set of 2 connected cages, each maintained at a different temperature using a water bath. One cage in each set was 20°C (Nesting cage; NC) while the other was one of 6 temperatures (Temperature cage; TC: 20, 23, 26, 29, 32, or 35°C). The NC contained one of 6 nesting provisions (0, 2, 4, 6, 8, or 10g), changed daily. Food intake and nest scores were measured in both cages. As the difference in temperature between paired cages increased, feed consumption in NC increased. Nesting provision altered differences in nest scores between the 2 paired temperatures. Nest scores in NC increased with increasing provision. In addition, temperature pairings altered the difference in nest scores with the smallest difference between locations at 26°C and 29°C. Mice transferred material from NC to TC but the likelihood of transfer decreased with increasing provision. Overall, mice of different strains and sexes prefer temperatures between 26-29°C and the shift from thermotaxis to nest building is seen between 6 and 10 g of material. Our results suggest that under normal laboratory temperatures, mice should be provided with no less than 6 grams of nesting material, but up to 10 grams may be needed to alleviate thermal distress under typical temperatures.