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BackgroundThis systematic review aimed to investigate whether the administration of hypnotic medicines, z-drugs, melatonin or benzodiazepines, reduced pain intensity postoperatively.MethodsMedline, 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.ResultsThe 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.ConclusionsThere 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 registrationThe protocol for this systematic review was registered with PROSPERO ID=CRD42015025327.

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.

We examined whether a polymorphism of the PERIOD3 gene (PER3; rs57875989) modulated the sleep promoting effects of melatonin in Delayed Sleep-Wake Phase Disorder (DSWPD). One hundred and four individuals (53 males; 29.4±10.0 years) with DSWPD and a delayed dim light melatonin onset (DLMO) collected buccal swabs for genotyping (PER34/4 n=43; PER3 5 allele [heterozygous and homozygous] n=60). Participants were randomised to placebo or 0.5mg melatonin taken 1 hour before desired bedtime (or ~ 1.45 h before DLMO), with sleep attempted at desired bedtime (4 weeks; 5-7 nights/week). We assessed sleep (diary and actigraphy), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Patient-Reported Outcomes Measurement Information System (PROMIS: Sleep Disturbance, Sleep-Related Impairment), Sheehan Disability Scale (SDS), and Patient- and Clinician-Global Improvement (PGI-C, CGI-C). Melatonin treatment response on actigraphic sleep onset time did not differ between genotypes. For PER34/4 carriers, self-reported sleep onset time was advanced by a larger amount and sleep onset latency (SOL) was shorter in melatonin-treated patients compared to those receiving placebo (P=0.008), while actigraphic sleep efficiency in the first third of the sleep episode (SE T1) did not differ. For PER3 5 carriers, actigraphic SOL and SE T1 showed a larger improvement with melatonin (P

Secondhand smoke (SHS) and physical inactivity are thought to be associated with type 2 diabetes mellitus (T2DM), but the synergistic effect of SHS with physical inactivity and their relationships with T2DM&ndash, associated inflammation biomarkers have not been estimated. We investigated the roles of SHS exposure and physical inactivity and their synergistic effect on T2DM risk and their relationships with T2DM associated inflammation biomarkers, neutrophil&ndash, lymphocyte ratio (NLR) and white blood cells (WBCs). A case&ndash, control study was conducted in total 588 participants (294 case T2DM and 294 healthy controls) from five community clinics in Indonesia. Participants completed a standardized questionnaire on demographic information, smoking status, physical activity habits and food consumption. WBCs and NLR levels were determined using an automated hematology analyzer. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were analyzed using multiple logistic regression model. The synergistic effect was analyzed using additive interaction for logistic regression. Physical inactive people exposed to SHS exhibited a synergistically increased 7.78-fold risk of T2DM compared with people who were not exposed to SHS and who were physically active. SHS is significantly correlated with a high NLR, WBCs and has a synergistic effect with physical inactivity on increasing susceptibility to T2DM.

There is growing interest in understanding how maternal diet might affect the sensitivity of offspring to environmental exposures. Previous studies demonstrated that adult rat offspring (approximately 6-months-old) from dams given a high-fat diet (HFD) prior to, during, and after pregnancy displayed elevated pulmonary responses to an acute ozone (O3) exposure. The aim of this study was to examine the influence of maternal and perinatal HFD on pulmonary and metabolic responses to O3 in male and female young-adult offspring (approximately 3-month old). One-month-old F0 female Long-Evans rats commenced HFD (60% kcal from fat) or control diet (CD; 10.5% kcal from fat) and were bred on PND 72. Offspring were maintained on respective HFD or CD until PND 29 when all groups were switched to CD. The 3-months-old female and male offspring (n = 10/group) were exposed to air or 0.8 ppm O3 for 5hr/day for 2 consecutive days. Maternal and perinatal HFD significantly increased body weight and body fat % in offspring regardless of gender. Ozone exposure, but not maternal and perinatal diet, induced hyperglycemia and glucose intolerance in the offspring. Ozone-induced alterations in pulmonary function were exacerbated by maternal and perinatal HFD in both offspring genders. Pulmonary injury/inflammation markers in response to O3 exposure such as bronchoalveolar lavage fluid total protein, lactate dehydrogenase, total cells, and neutrophils were further augmented in offspring (males>females) from dams fed the HFD. Data suggest that maternal and perinatal HFD may enhance the susceptibility of offspring to O3-induced pulmonary injury and that these effects may be sex-specific.

Background Depression is common in older people and is associated with underlying brain change increasing the risk of dementia. Sleep disturbance is frequently reported by those with lifetime depression, however whether circadian misalignment also exists is unclear. We aimed to examine circadian rhythms and sleep associations in older patients with and without lifetime depression. Methods Thirty-four older people meeting DSM-IV criteria for lifetime major depression (mean age = 63.9 years), and 30 healthy controls (mean age = 65.7 years) were recruited. Participants underwent 2-weeks of actigraphy followed by a 3-night protocol including dim light melatonin onset (DLMO) assessment and overnight polysomnography (PSG) for sleep architecture. DLMO and phase angle of entrainment were computed. Results Compared to controls, participants with depression had a significantly longer phase angle of entrainment (6.82 h ± 1.45 vs. 5.87 h ± 1.60, p = 0.02, Cohens-d = 0.62). A small to moderate yet non-significant difference in DLMO times, with earlier DLMO (34 ± 27 min) observed in depression (20:36 ± 1:48 vs. 21:10 ± 1:48, p = 0.22, Cohens-d = 0.32). Individuals with depression had longer sleep latency and latency to rapid eye movement sleep than controls (all p Conclusion Circadian advancement and alterations to the timing of sleep and REM onset are evident in older people with lifetime major depression, despite having only mild residual symptoms. Further research examining the prognostic significance of these changes is warranted as well as chronotherapeutic treatment studies.

The influence of maternal high-fat diet (HFD) on metabolic response to ozone was examined in Long-Evans rat offspring. F0 females were fed control diet (CD; 10%kcal from fat) or HFD (60%kcal from fat) starting at post-natal day (PND) 30. Rats were bred on PND 72. Dietary regimen was maintained until PND 30 when all offspring were switched to CD. On PND 40, F1 offspring (n = 10/group/sex) were exposed to air or 0.8 ppm ozone for 5 h. Serum samples were collected for global metabolomic analysis (n = 8/group/sex). Offspring from HFD dams had increased body fat and weight relative to CD. Metabolomic analysis revealed significant sex-, diet-, and exposure-related changes. Maternal HFD increased free fatty acids and decreased phospholipids (male > female) in air-exposed rats. Microbiome-associated histidine and tyrosine metabolites were increased in both sexes, while 1,5-anhydroglucitol levels decreased in males indicating susceptibility to insulin resistance. Ozone decreased monohydroxy fatty acids and acyl carnitines and increased pyruvate along with TCA cycle intermediates in females (HFD > CD). Ozone increased various amino acids, polyamines, and metabolites of gut microbiota in HFD female offspring indicating gut microbiome alterations. Collectively, these data suggest that maternal HFD increases offspring susceptibility to metabolic alterations in a sex-specific manner when challenged with environmental stressors.

Sleep staging is to score the sleep state of a subject into different sleep stages such as Wake and Rapid Eye Movement (REM) . It plays an indispensable role in the diagnosis and treatment of sleep disorders. As manual sleep staging through well-trained sleep experts is time consuming, tedious, and subjective, many automatic methods have been developed for accurate, efficient, and objective sleep staging. Recently, deep learning based methods have been successfully proposed for electroencephalogram (EEG) based sleep staging with promising results. However, most of these methods directly take EEG raw signals as input of convolutional neural networks (CNNs) without considering the domain knowledge of EEG staging. Apart from that, to capture temporal information, most of the existing methods utilize recurrent neural networks such as LSTM (Long Short Term Memory) which are not effective for modelling global temporal context and difficult to train. Therefore, inspired by the clinical guidelines of sleep staging such as AASM (American Academy of Sleep Medicine) rules where different stages are generally characterized by EEG waveforms of various frequencies, we propose a multi-scale deep architecture by decomposing an EEG signal into different frequency bands as input to CNNs. To model global temporal context, we utilize the multi-head self-attention module of the transformer model to not only improve performance, but also shorten the training time. In addition, we choose residual based architecture which makes training end-to-end. Experimental results on two widely used sleep staging datasets, Montreal Archive of Sleep Studies (MASS) and sleep-EDF datasets, demonstrate the effectiveness and significant efficiency (up to 12 times less training time) of our proposed method over the state-of-the-art.

Methods for predicting circadian phase have been developed for healthy individuals. It is unknown whether these methods generalize to clinical populations, such as delayed sleep–wake phase disorder (DSWPD), where circadian timing is associated with functional outcomes. This study evaluated two methods for predicting dim light melatonin onset (DLMO) in 154 DSWPD patients using ~ 7 days of sleep–wake and light data: a dynamic model and a statistical model. The dynamic model has been validated in healthy individuals under both laboratory and field conditions. The statistical model was developed for this dataset and used a multiple linear regression of light exposure during phase delay/advance portions of the phase response curve, as well as sleep timing and demographic variables. Both models performed comparably well in predicting DLMO. The dynamic model predicted DLMO with root mean square error of 68 min, with predictions accurate to within ± 1 h in 58% of participants and ± 2 h in 95%. The statistical model predicted DLMO with root mean square error of 57 min, with predictions accurate to within ± 1 h in 75% of participants and ± 2 h in 96%. We conclude that circadian phase prediction from light data is a viable technique for improving screening, diagnosis, and treatment of DSWPD.

Travel across time zones disrupts circadian rhythms causing increased daytime sleepiness, impaired alertness and sleep disturbance. However, the effect of repeated consecutive transmeridian travel on sleep-wake cycles and circadian dynamics is unknown. The aim of this study was to investigate changes in alertness, sleep-wake schedule and sleepiness and predict circadian and sleep dynamics of an individual undergoing demanding transmeridian travel. A 47-year-old healthy male flew 16 international flights over 12 consecutive days. He maintained a sleep-wake schedule based on Sydney, Australia time (GMT + 10 h). The participant completed a sleep diary and wore an Actiwatch before, during and after the flights. Subjective alertness, fatigue and sleepiness were rated 4 hourly (08:00-00:00), if awake during the flights. A validated physiologically based mathematical model of arousal dynamics was used to further explore the dynamics and compare sleep time predictions with observational data and to estimate circadian phase changes. The participant completed 191 h and 159 736 km of flying and traversed a total of 144 time-zones. Total sleep time during the flights decreased (357.5 min actigraphy; 292.4 min diary) compared to baseline (430.8 min actigraphy; 472.1 min diary), predominately due to restricted sleep opportunities. The daily range of alertness, sleepiness and fatigue increased compared to baseline, with heightened fatigue towards the end of the flight schedule. The arousal dynamics model predicted sleep/wake states during and post travel with 88% and 95% agreement with sleep diary data. The circadian phase predicted a delay of only 34 min over the 16 transmeridian flights. Despite repeated changes in transmeridian travel direction and flight duration, the participant was able to maintain a stable sleep schedule aligned with the Sydney night. Modelling revealed only minor circadian misalignment during the flying period. This was likely due to the transitory time spent in the overseas airports that did not allow for resynchronisation to the new time zone. The robustness of the arousal model in the real-world was demonstrated for the first time using unique transmeridian travel.

Sleep disturbances are one of the most frequent chief complaints brought to the healthcare professionals during routine prenatal care visits. Sleep and mood disturbances are often intertwined, and depression in particular is a leading cause of disability and disease burden worldwide with women more likely to be affected than men. However, limited studies have prospectively investigated the association between sleep disturbances and longitudinal risk of depression in pregnant women, with no studies using actigraphy to objectively estimate daytime and nighttime sleep duration and the extent of sleep disruption.To examine the predictive and longitudinal association of objective actigraphic and subjective sleep disturbances with depressive symptoms in pregnant women.A prospective observational cohort study.204 1st trimester pregnant women recruited from a university-affiliated hospital provided socio-demographic and health information, wore a wrist actigraph for 7 days, and completed Pittsburgh Sleep Quality Index, Center for Epidemiologic Studies - Depression Scale, and Epworth Sleepiness Scale. Identical data collection procedures were implemented again in the 2nd and 3rd trimester, with each data collection scheduled at least 8 weeks apart. We estimated unadjusted and multivariable adjusted odds ratios and 95% confidence intervals to evaluate various types of sleep disturbances at 1st trimester and risk of depression at follow-ups.121 (59.3%) 1st trimester women had a sleep efficiency of85% by actigraphy, and 92 (45.1%) had Pittsburgh Sleep Quality Index global scores5 indicative of poor sleep quality. In multivariable adjusted models, 1st trimester objectively measured sleep efficiency85% was associated with 2.71-, 3.87-, and 5.27-fold increased odds having risk of depression at 2nd trimester, 3rd trimester, and both 2nd and 3rd trimesters, respectively.Healthy pregnant women experience both objective and subjective sleep disturbances during the early trimester, with a substantial proportion of them also having high depressive symptoms throughout the pregnancy. Objectively assessed poor sleep quality in the 1st trimester, but not self-reported characteristics of disturbed sleep, may play a role in the development of both elevated and persistent high depressive symptoms in pregnancy. Future studies using objective sleep measurements and clinical diagnostic interviews are warranted to examine whether an early intervention aiming at improving sleep may help reduce high depressive symptom risk and lower depression rate in women during pregnancy. Tweetable abstract: Objectively assessed poor sleep efficiency in the 1st trimester predicts both elevated and persistent high depressive symptoms in pregnancy.

While disturbances of the sleep-wake cycle are common in people with affective disorders, the characteristics of these disturbances differ greatly between individuals. This heterogeneity is likely to reflect multiple underlying pathophysiologies, with different perturbations in circadian systems contributing to the variation in sleep-wake cycle disturbances. Such disturbances may be particularly relevant in adolescents and young adults with affective disorders as circadian rhythms undergo considerable change during this key developmental period. This study aimed to identify profiles of sleep-wake disturbance in young people with affective disorders and investigate associations with biological circadian rhythms. Fifty young people with affective disorders and 19 control participants (aged 16-31 years) underwent actigraphy monitoring for approximately two weeks to derive sleep-wake cycle parameters, and completed an in-laboratory assessment including evening dim-light saliva collection for melatonin assay and overnight continuous core body temperature measurement. Cluster analysis based on sleep-wake cycle parameters identified three distinct patient groups, characterised by 'delayed sleep-wake', 'disrupted sleep', and 'long sleep' respectively. The 'delayed sleep-wake' group had both delayed melatonin onset and core temperature nadir; whereas the other two cluster groups did not differ from controls on these circadian markers. The three groups did not differ on clinical characteristics. These results provide evidence that only some types of sleep-wake disturbance in young people with affective disorders are associated with fundamental circadian perturbations. Consequently, interventions targeting endogenous circadian rhythms to promote a phase shift may be particularly relevant in youth with affective disorders presenting with delayed sleep-wake cycles.

Epidemiological and experimental data suggest that obesity exacerbates the health effects of air pollutants such as ozone (O3). Maternal inactivity and calorically rich diets lead to offspring that show signs of obesity. Exacerbated O3 susceptibility of offspring could thus be manifested by maternal obesity. Thirty-day-old female Long-Evans rats were fed a control (CD) or high-fat (HF) (60% calories) diet for 6 wks and then bred. GD1 rats were then housed with a running wheel (RW) or without a wheel (SED) until parturition, creating four groups of offspring: CD-SED, CD-RW, HF-SED and HF-RW. HF diet was terminated at PND 35 and all offspring were placed on CD. Body weight and %fat of dams were greatest in order; HF-SED > HF-RW > CD-SED > CD-RW. Adult offspring were exposed to O3 for two consecutive days (0.8 ppm, 4 h/day). Glucose tolerance tests (GTT), ventilatory parameters (plethysmography), and bronchoalveolar fluid (BALF) cell counts and protein biomarkers were performed to assess response to O3. Exercise and diet altered body weight and %fat of young offspring. GTT, ventilation and BALF cell counts were exacerbated by O3 with responses markedly exacerbated in males. HF diet and O3 led to significant exacerbation of several BALF parameters: total cell count, neutrophils and lymphocytes were increased in male HF-SED versus CD-SED. Males were hyperglycemic after O3 exposure and exhibited exacerbated GTT responses. Ventilatory dysfunction was also exacerbated in males. Maternal exercise had minimal effects on O3 response. The results of this exploratory study suggest a link between maternal obesity and susceptibility to O3 in their adult offspring in a sex-specific manner.

BACKGROUND Previous studies examining insomnia in populations with traumatic brain injury (TBI) have not distinguished between transient insomnia symptoms and insomnia disorder and associations have been confounded by other highly prevalent sleep disorders post-TBI. OBJECTIVE To investigate the associations between affective symptoms and somatoform symptoms in patients with TBI and insomnia, sleep apnoea and hypersomnolence. METHODS Twenty-four participants from a multidisciplinary brain injury rehabilitation service with TBI were assessed for insomnia disorder, using Diagnostic and Statistical Manual Fifth Edition (DSM-5) criteria. Associations with affective and somatic symptoms were assessed, using the DASS-21 and PHQ-15 respectively. The same cohort was divided for Obstructive Sleep Apnoea (OSA) and hypersomnolence and analysed for the same outcomes. Associations were assessed using Pearson's correlation and a logistic binary regression model was developed to predict insomnia in patients with brain injury. RESULTS The insomnia disorder group (n = 11) had significantly higher rates somatoform symptoms (p

The aim of this meta-analysis was to compare the pooled sensitivity and specificity of the Pediatric Sleep Questionnaire (PSQ), Obstructive Sleep Apnea Questionnaire (OSA-18), and pulse oximetry (PO) according to OSAS severity. Three electronic databases were searched for studies evaluating sensitivity and specificity of the three tools against the apnea-hypopnea index measured using overnight in-laboratory or in-home polysomnography in children and adolescents from inception until January 11, 2020. A random-effects bivariate model was used to estimate the summary sensitivity and specificity of the tools. We identified 39 studies involving 6131 clinical and community children (aged 2.9-16.7 y). The PSQ exhibited the highest sensitivity (74%) for detecting symptoms of mild pediatric OSAS. The PSQ and PO had comparable sensitivity in screening moderate and severe pediatric OSAS (0.82 and 0.89 vs 0.83 and 0.83, respectively). PO yielded superior specificity in detecting mild, moderate, and severe pediatric OSAS (86%, 75%, and 83%, respectively) than did the PSQ and OSA-18 (all p 0.05). Age, percentage of girls, index test criteria, methodology quality, and sample size significantly moderated sensitivity and specificity. For early detection of pediatric OSAS, the combined use of PSQ and PO is recommended when polysomnography is not available. PROSPERO REGISTRATION NUMBER: CRD42018090571.

Importance: Digital cognitive behavioral therapy (dCBT) is a scalable and effective intervention for treating insomnia. Most people with insomnia, however, seek help because of the daytime consequences of poor sleep, which adversely affects quality of life. Objectives: To investigate the effect of dCBT for insomnia on functional health, psychological well-being, and sleep-related quality of life and to determine whether a reduction in insomnia symptoms was a mediating factor. Design, Setting, and Participants: This online, 2-arm, parallel-group randomized trial comparing dCBT for insomnia with sleep hygiene education (SHE) evaluated 1711 participants with self-reported symptoms of insomnia. Participants were recruited between December 1, 2015, and December 1, 2016, and dCBT was delivered using web and/or mobile channels plus treatment as usual; SHE comprised a website and a downloadable booklet plus treatment as usual. Online assessments took place at 0 (baseline), 4 (midtreatment), 8 (posttreatment), and 24 (follow-up) weeks. Programs were completed within 12 weeks after inclusion. Main Outcomes and Measures: Primary outcomes were scores on self-reported measures of functional health (Patient-Reported Outcomes Measurement Information System: Global Health Scale; range, 10-50; higher scores indicate better health); psychological well-being (Warwick-Edinburgh Mental Well-being Scale; range, 14-70; higher scores indicate greater well-being); and sleep-related quality of life (Glasgow Sleep Impact Index; range, 1-100; higher scores indicate greater impairment). Secondary outcomes comprised mood, fatigue, sleepiness, cognitive failures, work productivity, and relationship satisfaction. Insomnia was assessed with the Sleep Condition Indicator (range: 0-32; higher scores indicate better sleep). Results: Of the 1711 participants included in the intention-to-treat analysis, 1329 (77.7%) were female, mean (SD) age was 48.0 (13.8) years, and 1558 (91.1%) were white. Use of dCBT was associated with a small improvement in functional health compared with SHE (adjusted difference [95% CI] at week 4, 0.90 [0.40-1.40]; week 8, 1.76 [1.24-2.28]; week 24, 1.76 [1.22-2.30]) and psychological well-being (adjusted difference [95% CI] at week 4, 1.04 [0.28-1.80]; week 8, 2.68 [1.89-3.47]; week 24, 2.95 [2.13-3.76]), and with a large improvement in sleep-related quality of life (at week 4, -8.76 [-11.83 to -5.69]; week 8, -17.60 [-20.81 to -14.39]; week 24, -18.72 [-22.04 to -15.41]) (all P Conclusions and Relevance: Use of dCBT is effective in improving functional health, psychological well-being, and sleep-related quality of life in people reporting insomnia symptoms. A reduction in insomnia symptoms mediates these improvements. These results confirm that dCBT improves both daytime and nighttime aspects of insomnia, strengthening existing recommendations of CBT as the treatment of choice for insomnia. Trial Registration: isrctn.org identifier: ISRCTN60530898.

Mouse vivaria are typically maintained at an ambient temperature (Ta) of 20–26 °C which is comfortable for human researchers. However, as this Ta is well below the mouse thermoneutral zone (TNZ) of 30–32 °C, typical vivarium temperatures result in cold stress for mice. Recently, a cage has been developed that provides variable cage floor heating, allowing mice to behaviorally regulate body temperature through thermotaxis. A hand warmer provides supplemental heat, elevating cage floor surface temperature for 13 + hours up to 30 °C. This provides a heated surface for the entirety of the light phase. Here, we test the ability of these local heat sources to remove physiological signs of cold stress in mice housed at room temperature by analyzing heart rate (HR), activity, and body temperature in three experimental conditions: 23 °C, 23 °C + heated surface, or 30 °C. The location of C57Bl/6 J mice within the cage was recorded using an infrared camera. In the presence of supplemental heat at a Ta of 23 °C, mice resided atop of the area of the heated surface 85 ± 3% of the 12-h light phase, as compared to 7 ± 2% in the absence of supplemental heat. Further, addition of supplemental heat lowered light phase HR and activity to that seen at a Ta of 30 °C. These results indicate that provision of a local heat source is successful in reducing cold-induced tachycardia in mice housed at typical vivarium temperatures without increasing the ambient temperature of the entire laboratory and subjecting researchers to heat stress.

Background: In healthy populations, irregular sleep patterns are associated with delayed sleep and poor functional/mood outcomes. Currently, it is unknown whether irregular sleep contributes to poor functional/mood outcomes in individuals with Delayed Sleep-Wake Phase Disorder (DSWPD). Methods: In 170 patients with DSWPD, we collected sleep-wake patterns, dim light melatonin onset (DLMO), and functional/mood outcomes. The Sleep Regularity Index (SRI)and other sleep timing metrics were computed. Correlations of SRI were computed with phase angle (difference between DLMO and desired bedtime), sleep timing and quality variables, daytime function, sleep-related daytime impairment, mood, and insomnia symptom severity. Path analyses assessed whether SRI or total sleep time mediated the associations between sleep onset time and phase angle with daytime functioning, sleep-related impairment, and mood outcomes. Results: Higher SRI was associated with earlier sleep and longer total sleep time, but did not relate to sleep quality, daytime function, or mood outcomes. Path analysis showed that phase angle was directly associated with all outcome variables, whereas sleep onset time was not directly associated with any. SRI mediated the effects of sleep onset time and phase angle on daytime function. Total sleep time mediated the effects of sleep onset time and phase angle on sleep-related impairment. Conclusion: Individuals with DSWPD who have more delayed sleep and a greater phase angle also have more irregular sleep. This suggests that it is not delayed sleep timing per se that drives poor functional outcomes in DSWPD, but rather the timing of sleep relative to circadian phase and resultant irregular sleep patterns. © 2019 Elsevier B.V.

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

Australia has an increasing demand for a sustainable primary health care registered nursing workforce. Targeting graduate registered nurses who typically begin their nursing career in acute-care hospital settings is a potential workforce development strategy. We evaluated a graduate registered nurse Community Transition to Professional Practice Program which was designed specifically to develop and foster skills required for primary health care. The aims of this study were to evaluate graduates' intention to remain in the primary health care nursing workforce, and graduate competency, confidence and experiences of program support; these were compared with graduates undertaking the conventional acute-care transition program. Preceptor ratings of graduate competence were also measured. All of the 25 graduates (n = 12 community, n = 13 acute-care) who completed the questionnaire at 6 and 12 months intended to remain in nursing, and 55% (n = 6) of graduates in the Community Transition Program intended to remain in the primary health care nursing workforce. There were no differences in graduate experiences, including level of competence, or preceptors' perceptions of graduate competence, between acute-care and Community Transition Programs. The Community Transition to Professional Practice program represents a substantial step towards developing the primary health care health workforce by facilitating graduate nurse employment in this area.

Objectives To evaluate brain metabolites in objective insomnia subtypes defined from polysomnography (PSG): insomnia with short sleep duration (I-SSD) and insomnia with normal sleep duration (I-NSD), relative to good sleeping controls (GSCs). Methods PSG empirically grouped insomnia patients into I-SSD (n = 12: mean [SD] total sleep time [TST] = 294.7 minutes [30.5]) or I-NSD (n = 19: TST = 394.4 minutes [34.9]). 1H magnetic resonance spectroscopy (MRS) acquired in the left occipital cortex (LOCC), left prefrontal cortex, and anterior cingulate cortex was used to determine levels of creatine, aspartate, glutamate, and glutamine (referenced to water). Glutathione, glycerophosphocholine, lactate, myoinositol, and N-acetylaspartate measurements were also obtained. Sixteen GSCs were included for comparison. Multivariate analysis of variance was used to evaluate differences in creatine, aspartate, glutamate, and glutamine. Results Aspartate and glutamine concentrations were reduced in the LOCC in I-SSD compared with I-NSD (both p < .05, d = .80-.99). Creatine displayed a nonsignificant mean reduction in I-SSD compared with I-NSD (p = .05, d = .58). Glutamine was reduced in I-SSD compared with controls (p < .05, d = .93). There were no differences in metabolites between all (I-SSD and I-NSD) insomnia patients and controls. In patients with insomnia, LOCC glutamine concentrations were found to be positively correlated with TST (r = .43, p < .05) and negatively correlated with wake-time after sleep onset (r = -.40, p < .05). Conclusions Results indicate that I-SSD is associated with reduced brain metabolites in the LOCC compared with I-NSD and control concentrations of aspartate, glutamine, and creatine. Clinical Trial Registration Insomnia MRS imaging sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000050853. Trial Identification Number 12612000050853.

Aim: Few investigators have considered the possibility that skeletal muscles might contain thermosensitive elements capable of modifying thermoeffector responses. In this experiment, the temporal relationships between dynamic changes in deep-body and intramuscular temperatures and eccrine sweat secretion were explored during rhythmical and reproducible variations in heat production. Methods: Eight subjects performed semi-recumbent cycling (25 °C) at a constant load to first establish whole-body thermal and sudomotor steady states (35 min), followed by a 24-min block of sinusoidal workload variations (three, 8-min periods) and then returning to steady-state cycling (20 min). Individual oesophageal, mean skin and intramuscular (vastus lateralis) temperatures were independently cross-correlated with simultaneously measured forehead sweat rates to evaluate the possible thermal modulation of sudomotor activity. Results: Both intramuscular and oesophageal temperatures showed strong correlations with sinusoidal variations in sweating with respective maximal cross-correlation coefficients of 0.807 ( 0.044) and 0.845 ( 0.035), but these were not different (P = 0.40). However, the phase delay between intramuscular temperature changes and sweat secretion was significantly shorter than the delay between oesophageal temperature and sweating [25.6 s ( 12.6) vs. 46.9 s ( 11.3); P = 0.03]. Conclusion: The temporal coupling of eccrine sweating to intramuscular temperature, combined with a shorter phase delay, was consistent with the presence of thermosensitive elements within skeletal muscles that appear to participate in the modulation of thermal sweating. Refereed/Peer-reviewed

Setting exposure standards for environmental pollutants may consider the aged as a susceptible population but the few published studies assessing susceptibility of the aged to air pollutants are inconsistent. Episodic ozone (O-3) is more reflective of potential exposures occurring in human populations and could be more harmful to the aged. This study used radiotelemetry to monitor heart rate (HR), core temperature (T-c) and motor activity (MA) in adult (9-12 months) and senescent (20-24 months) male, Brown Norway rats exposed to episodic O-3 (6 h/day of 1 ppm O-3 for 2 consecutive days/week for 13 weeks). Acute O-3 initially led to marked drops in HR and T-c. As exposures progressed each week, there was diminution in the hypothermic and bradycardic effects of O-3. Senescent rats were less affected than adults. Acute responses were exacerbated on the second day of O-3 exposure with adults exhibiting greater sensitivity. During recovery following 2 d of O-3, adult and senescent rats exhibited an elevated Tc and HR during the day but not at night, an effect that persisted for at least 48 h after O-3 exposure. MA was elevated in adults but not senescent rats during recovery from O-3. Overall, acute effects of O-3, including reductions in HR and T-c, were attenuated in senescent rats. Autonomic responses during recovery, included an elevation in T-c with a pattern akin to that of a fever and rise in HR that were independent of age. An attenuated inflammatory response to O-3 in senescent rats may explain the relatively heightened physiological response to O-3 in younger rats.

Background: High occupational stress has been associated with altered eating behaviors and obesity. Occupational stress is reported to be high in Asian countries. Furthermore, many Asian countries are increasingly consuming Western-type foods (e.g., incorporating drinks with meals) which collectively may also be contributing to obesity. Therefore, the aim of this study was to examine (a) associations between sugar-sweetened beverage (SSB) consumption as meal replacement and obesity and (b) associations between workload and substituting meals with SSB in nurses. Methods: A representative sample of 854 hospital-based nurses completed a structured questionnaire about SSB consumption, workload, and body mass index (BMI). Log binomial regression models were employed to test associations between SSBs and obesity rates and associations between workload and SSBs. Results: Most participants (57.6%) consumed SSBs as meal replacements during work. This was related to high workloads during shifts. Substituting SSBs for meals was significantly associated with increased likelihood of obesity (aPRR = 1.4, 95% CI (1.1, 1.7)). Workload was positively associated with SSB intake as meal substitutes (aPRR = 1.4, 95% CI (1.2, 1.6)). Conclusions: Our findings show that SSBs are used as meal substitutes and is due to the workload demands. Sugar-sweetened beverage consumption is also positively associated with the increased likelihood of obesity. Interventions that modify workloads and decrease SSB consumption may improve workers&rsquo, eating behaviors and health.

Adverse intrauterine environments have been associated with increased risk of later cardiovascular disease and hypertension. In an animal model using diverse developmental toxicants, we measured blood pressure (BP), renal nephron endowment, renal glucocorticoid receptor (GR) gene expression, and serum aldosterone in offspring of pregnant Sprague Dawley rats exposed to dexamethasone (Dex), perfluorooctane sulfonate (PFOS), atrazine, perfluorononanoic acid (PFNA), arsenic, or nicotine. BP was assessed by tail cuff photoplethysmography, nephron endowment by confocal microscopy, and renal GR mRNA by qPCR. BP was also measured by telemetry, and corticosterone (CORT) was measured in resting or restrained Dex and atrazine offspring. Treated dams gained less weight during treatment in all groups except arsenic. There were chemical- and sex-specific effects on birth weight, but offspring body weights were similar by weaning. BP was higher in Dex, PFOS, atrazine, and PFNA male offspring by 7-10 weeks. Female offspring exhibited elevated BP at 10 weeks for PFNA and arsenic, and at 37 weeks for Dex, PFOS, and atrazine. Dex, PFOS, and atrazine offspring still exhibited elevated BP at 52-65 weeks of age; others did not. Elevated BP was associated with lower nephron counts. Dex, PFOS, and atrazine offspring had elevated renal GR gene expression. Elevations in BP were also observed in Dex and atrazine offspring by radiotelemetry. Atrazine offspring exhibited enhanced CORT response to restraint. Elevated offspring BP was induced by maternal exposure to toxicants. Because all treatments affected maternal gestational weight gain, maternal stress may be a common underlying factor in these observations.

In laboratories, mice are housed at 20-24 °C, which is below their lower critical temperature (≈30 °C). Thus, mice are potentially cold stressed, which can alter metabolism, immune function, and reproduction. These physiological changes reflect impaired wellbeing, and affect scientific outcomes. We hypothesized that nesting material would allow mice to alleviate cold stress by controlling their thermal microenvironment, thus insulating them, reducing heat loss and thermogenic processes. Naïve C57BL/6, CD-1, and BALB/c mice (24 male and 24 female/strain in groups of 3) were housed in standard cages at 20 °C either with or without 8 g nesting material for 4 weeks. Core body temperature was followed using intraperitoneal radio telemetry. The thermal properties of the nests were assessed using a thermal imaging camera, and related to nest quality. Higher scoring nests were negatively correlated with the mean radiated temperature and were thus more insulating. No effects of nesting material on body temperature were found. CD-1 mice with nesting material had higher end body weights than controls. No effect was seen in the other two strains. Mice with the telemetry implant had larger spleens than controls, possibly indicating an immune response to the implant or low level infection from the surgery. BALB/c mice express less mRNA for the UCP1 protein than mice without nesting material. This indicates that BALB/c's with nesting material do not utilize their brown fat to create heat as readily as controls. Nests can alleviate thermal discomfort by decreasing the amount of radiated heat and reduce the need for non-shivering thermogenesis. However, different strains appear to use different behavioral (through different primary modes of behavioral thermoregulation) and physiological strategies (utilizing thermogenesis to different degrees) to maintain a constant body temperature under cool standard laboratory ambient temperatures.

Study Objective: To examine the prevalence of circadian misalignment in clinically diagnosed delayed sleep phase disorder (DSPD) and to compare mood and daytime functioning in those with and without a circadian basis for the disorder. Methods: One hundred and eighty-two DSPD patients aged 16-64 years, engaged in regular employment or school, underwent sleep-wake monitoring in the home, followed by a sleep laboratory visit for assessment of salivary dim light melatonin onset (DLMO). Based on the DLMO assessments, patients were classified into two groups: circadian DSPD, defined as DLMO occurring at or after desired bedtime (DBT), or non-circadian DSPD, defined as DLMO occurring before DBT. Results: One hundred and three patients (57%) were classified as circadian DSPD and 79 (43%) as non-circadian DSPD. DLMO occurred 1.66 hours later in circadian DSPD compared to non-circadian DSPD (p < .001). Moderate-severe depressive symptoms (Beck Depression Inventory-II) were more prevalent in circadian DSPD (14.0%) than in non-circadian DSPD (3.8%; p < .05). Relative to non-circadian DSPD patients, circadian DSPD patients had 4.31 times increased odds of at least mild depressive symptoms (95% CI 1.75 to 10.64; p < .01). No group differences were found for daytime sleepiness or function, but DSPD symptoms were rated by clinicians to be more severe in those with circadian DSPD. Conclusions: Almost half of patients clinically diagnosed with DSPD did not show misalignment between the circadian pacemaker and the DBT, suggesting that the reported difficulties initiating sleep at the DBT are unlikely to be explained by the (mis)timing of the circadian rhythm of sleep propensity. Circadian misalignment in DSPD is associated with increased depressive symptoms and DSPD symptom severity.

Background Registered nurses are under-represented in the primary health care setting both internationally and in Australia, and this shortage is predicted to worsen. To address the increasingly complex healthcare needs of an ageing population, it is vital to develop and sustain a primary health care nursing workforce, yet attracting nurses is challenging. In Australia, registered nurses graduating from university typically commence their careers in hospital-based transition to professional practice programs. Similar programs in primary health care settings may be a valuable strategy for developing the primary health care nursing workforce, yet little is known about nursing students desire to work in this setting, factors that influence this, or their expectations of primary health care-focused transition to professional practice programs. Objectives This study sought to identify factors associated with final year nursing students' desire to work in primary health care setting including demographic factors, expectations of future employment conditions, and job content. It also explored expectations of graduate transition programs based in primary health care. Design A cross-sectional survey design comprising a quantitative online survey. Setting 14 Australian universities from all states/territories, both rural and urban. Participants 530 final-year nursing students. Methods Binary logistic regression identifying factors contributing to desire to work in primary health care. Results The desire of nursing students to work in primary health care is associated with older age, greater perceived value of employment conditions including flexibility, and less perceived importance of workplace support. Conclusions Collaborative efforts from primary health care nurses, health professionals, academics and policy makers are needed to attract new graduate nurses to primary health care.

Background Teamwork training is an essential component of health professional student education. A valid and reliable teamwork self-assessment tool could assist students to identify desirable teamwork behaviours with the potential to promote learning about effective teamwork. The aim of this study was to develop and evaluate a self-assessment teamwork tool for health professional students for use in the context of emergency response to a mass casualty. Methods The authors modified a previously published teamwork instrument designed for experienced critical care teams for use with medical and nursing students involved in mass casualty simulations. The 17-item questionnaire was administered to students immediately following the simulations. These scores were used to explore the psychometric properties of the tool, using Exploratory and Confirmatory Factor Analysis. Results 202 (128 medical and 74 nursing) students completed the self-assessment teamwork tool for students. Exploratory factor analysis revealed 2 factors (5 items - Teamwork coordination and communication; 4 items - Information sharing and support) and these were justified with confirmatory factor analysis. Internal consistency was 0.823 for Teamwork coordination and communication, and 0.812 for Information sharing and support. Conclusions These data provide evidence to support the validity and reliability of the self-assessment teamwork tool for students This self-assessment tool could be of value to health professional students following team training activities to help them identify the attributes of effective teamwork. Electronic supplementary material The online version of this article (doi:10.1186/s12909-016-0743-9) contains supplementary material, which is available to authorized users.

Body fat serves as a storage compartment for lipophilic pollutants and affects the pharmacokinetics of many toxic chemicals. Understanding how body fat varies with gender, strain, and age may be essential for development of experimental models to study mechanisms of toxicity. Nuclear magnetic resonance (NMR)-based analysis serves as a noninvasive means of assessing proportions of fat, lean, and fluid in rodents over their lifetime. The aim of this study was to track changes in body composition of male and female Long-Evans (LE), Sprague-Dawley (SD), Fischer (F334), and Brown Norway (BN) rats from postweaning over a >2-yr period. Percent fat of preweaned LE and SD rats was markedly higher compared to the other strains. LE and SD strains displayed marked increases in body fat from weaning to 8 mo of age. Postweaned F344 male and females showed relatively low levels of percent fat; however, at 2 yr of age percent fat of females was equal to that of SD and LE in females. BN rats showed the highest levels of lean tissue and lowest levels of fat. Percent fat of the BN strain rose at the slowest rate as they aged. Percent fluid was consistently higher in males for all strains. Females tended to have higher percent fat than males in LE, SD, and F344 strains. Assessing changes in body fat as well as lean and fluid of various strains of male and female rats over their lifetime may prove useful in many research endeavors, including pharmacokinetics of lipophilic toxicants, mechanisms underlying obesity, and metabolic disorders.

Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25 and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects. Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers of pulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that adolescent and young adult animals are more susceptible to changes in ventilation and pulmonary injury/inflammation caused by acute and episodic O3 exposure.

Simulation-based clinical education often aims to replicate varying aspects of real clinical practice. It is unknown whether learners' stress levels in simulation are comparable with those in clinical practice. The current study compared acute stress markers during simulation-based clinical education with that experienced in situ in a hospital-based environment.Undergraduate physiotherapy students' (n = 33) acute stress responses [visual analog scales of stress and anxiety, continuous heart rate (HR), and saliva cortisol] were assessed during matched patient encounters in simulation-based laboratories using standardized patients and during hospital clinical placements with real patients. Group differences in stress variables were compared using repeated measures analysis of variance for 3 time points (before, during the patient encounter, and after) at 2 settings (simulation and hospital).Visual analog scale stress and anxiety as well as HR increased significantly from baseline levels before the encounter in both settings (all P0.05). Stress and anxiety were significantly higher in simulation [mean (SD), 45 (22) and 44 (25) mm; P = 0.003] compared with hospital [mean (SD), 31 (21) and 26 (20) mm; P = 0.002]. The mean (SD) HR during the simulation patient encounter was 90 (16) beats per minute and was not different compared with hospital [mean (SD), 87 (15) beats per minute; P = 0.89]. Changes in salivary cortisol before and after patient encounters were not statistically different between settings [mean (SD) simulation, 1.5 (2.4) nmol/L; hospital, 2.5 (2.9) nmol/L; P = 0.70].Participants' experienced stress on clinical placements, irrespective of the clinical education setting (simulation vs. hospital). This study revealed that psychological stress and anxiety were greater during simulation compared with hospital settings; however, physiological stress responses (HR and cortisol) were comparable. These results indicate that psychological stress may be heightened in simulation, and health professional educators need to consider the impact of this on learners in simulation-based clinical education. New learners in their clinical education program may benefit from a less stressful simulation environment, before a gradual increase in stress demands as they approach clinical practice.

Serum biomarkers to identify susceptibility to disease in aged humans are well researched. On the other hand, our understanding of biomarkers in animal models of aging is limited. Hence, we applied a commercially available panel of 58 serum analytes to screen for possible biomarkers of aging in 4, 12, and 24 month old Brown Norway rats. We found that serum levels of 5 of the 58 analytes were significantly affected by age: C-reactive protein (CRP), myoglobin, macrophage derived chemokine-2 (MDC), fibroblast growth factor-basic, and vascular cell adhesion molecule-1. Among these analytes, CRP was the only one that increased with aging. The variability of CRP and MDC-2 was relatively low compared to the other analytes of the panel. It is concluded that CRP and possibly MDC-2 are candidates for biomarkers of aging in the BN rat.

Recent research on the acute effects of volatile organic compounds suggests that extrapolation from short (∼1 h) to long durations (up to 4 h) may be improved by using estimates of brain toluene concentration (Br[Tol]) instead of cumulative inhaled dose (C × t) as a metric of dose. This study compared predictions of these two dose metrics on the acute behavioral effects of inhaled toluene in rats during exposures up to 24 h in duration. We first evaluated estimates of Br[Tol] with a physiologically based toxicokinetic (PBTK) model for rats intermittently performing an operant task while inhaling toluene for up to 24 h. Exposure longer than 6 h induced P450-mediated metabolism of toluene. Adjusting the corresponding parameters of the PBTK model improved agreement between estimated and observed values of Br[Tol] in the 24-h exposure scenario. Rats were trained to perform a visual signal detection task and were then tested while inhaling toluene (0, 1125, and 1450 ppm for 24 h and 1660 ppm for 21 h). Tests occurred at times yielding equivalent C × t products but different estimates of Br[Tol], and also at 1 and 6 h afterexposure. Effects of toluene were better predicted by Br[Tol] than by C × t. However, even using Br[Tol] as the dose metric (after accounting for metabolic induction), acute dose-effect functions during 24-h exposures were shifted to the right relative to 1-h exposures, indicating that a dynamic behavioral tolerance also developed during prolonged exposure to toluene.

Parathyroid hormone (PTH) nomograms combine total calcium and intact PTH (iPTH) measurements to classify disorders of calcium homeostasis. Our objective was to determine if using a combination of laboratory, demographic, and clinical parameters improves the accuracy of classification of these disorders. Chart data were collected for 236 patients with physician-ordered iPTH and total calcium tests. Classification was done using 3 approaches: (1) PTH nomogram plotting total calcium and iPTH results against known cases; (2) review of all available chart data (“gold standard”); and (3) multivariate model (classification and regression tree [CART] or logistic regression) using 24 variables. The CART model was developed using the gold standard patient classification and validated using leave-one-out cross-validation. The CART model was significantly (P = .002) more accurate (80.6%) than the PTH nomogram (59.7%) and logistic regression (66.2%) at classifying calcium homeostasis disorders. The CART model used 6 of 24 variables (iPTH, calcium, creatinine, renal transplantation, percentage of females, and urea nitrogen) and had a misclassification error rate of 0.194 (27/139). Classification of disorders of calcium homeostasis based on the PTH nomogram can be improved by using the CART model developed in this study.

The typical core temperature (Tc) profile displayed during heatstroke (HS) recovery consists of initial hypothermia followed by delayed hyperthermia. Anecdotal observations led to the conclusion that these Tc responses represent thermoregulatory dysfunction as a result of brain damage. We hypothesized that these Tc responses are mediated by a change in the temperature setpoint. Tc (± 0.1°C; radiotelemetry) of male C57BL/6J mice was monitored while they were housed in a temperature gradient with ambient temperature (Ta) range of 20–39°C to monitor behaviorally selected Ta (Ts) or an indirect calorimeter (Ta = 25°C) to monitor metabolism (V̇o2) and calculate respiratory exchange ratio (RER). Responses to mild and severe HS (thermal area 249.6 ± 18.9 vs. 299.4 ± 19.3°C·min, respectively) were examined through 48 h of recovery. An initial hypothermia following mild HS was associated with warm Ts (∼32°C), ∼35% V̇o2 decrease, and RER ∼0.71 that indicated reliance on fatty acid oxidation. After 24 h, mild HS mice developed hyperthermia associated with warm Ts (∼32°C), ∼20% V̇o2 increase, and RER ∼0.85. Severe HS mice appeared poikilothermic-like in the temperature gradient with Tc similar to Ts (∼20°C), and these mice failed to recover from hypothermia and develop delayed hyperthermia. Cellular damage (hematoxylin and eosin staining) was undetectable in the hypothalamus or other brain regions in severe HS mice. Overall, decreases and increases in Tc were associated with behavioral and autonomic thermoeffectors that suggest HS elicits anapyrexia and fever, respectively. Taken together, Tc responses of mild and severe HS mice suggest a need for reinterpretation of the mechanisms of thermoregulatory control during recovery.

Background Delayed 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). Methods This 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. Findings Between 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. Conclusions In 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 registration This trial was registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000425897., In this randomized trial, Tracey L Sletten demonstrate sleep-promoting effects of melatonin combined with behavioral sleep-wake scheduling in participants with Delayed Sleep-Wake Phase Disorder., Author summary Why was this study done? Circadian disruption—and Delayed Sleep-Wake Phase Disorder (DSWPD) specifically—is associated with significant morbidity, including depression, poor academic and work performance, and adverse social and economic outcomes. Previous studies examining treatments for DSWPD have typically diagnosed the disorder based on sleep symptomology, not circadian timing, which may result in misdiagnosis of sleep initiation insomnia as DSWPD and thus inappropriate treatment. Although exogenous melatonin has been widely advocated as a treatment for DSWPD, the therapeutic potential of the sleep-promoting effects of melatonin have not been evaluated rigorously in a randomised controlled trial in well-characterised DSWPD patients. What did the researchers do and find? DSWPD patients (n = 116) with a delayed melatonin rhythm relative to patient desired bedtime (DBT) completed a 4-wk trial of melatonin (0.5 mg) or placebo administered 1 h prior to DBT, combined with a behavioural sleep-wake intervention consisting of attempting sleep at the patient DBT for at least 5 nights per week. Relative to baseline, sleep onset time was 34 min earlier, sleep efficiency during the first tertile of sleep (SE T1) was greater, and sleep-related functional impairment was lower in the melatonin group compared to placebo. Sleep disturbance, insomnia severity, and functional disability decreased, and a greater proportion of patients showed clinician-rated improvement following melatonin treatment (52.8%) compared to placebo (24.0%). The observed improvements in sleep were clinically significant according to clinical practice guidelines for the treatment of circadian rhythm sleep disorders and compared to other established therapeutic approaches. What do the findings mean? Melatonin treatment, when combined with behavioural sleep-wake scheduling, is efficacious for improving sleep disturbances and sleep-related impairments in DSWPD patients and potentially in other patients who show abnormal circadian timing relative to sleep. Current melatonin treatment protocols for DSWPD vary in patient diagnostic criteria; vary in the dose, formulation, and timing of melatonin; and may result in low compliance due to the requirement for strict adherence every day. These findings contribute to the evidence base to improve the diagnosis of DSWPD and the development of a standardised treatment protocol.

Aging adults are a growing segment of the U.S. population and are likely to exhibit increased susceptibility to many environmental toxicants. However, there is little information on the susceptibility of the aged to toxicants. The toxicity of toluene has been well characterized in young adult rodents but there is little information in the aged. Three approaches were used: (1) pharmacokinetic (PK), (2) cardiac biomarkers, and (3) whole-animal physiology to assess whether aging increases susceptibility to toluene in the Brown Norway (BN) rat. Three life stages, young adult, middle aged, and aged (4, 12, and 24 mo, respectively), were administered toluene orally at doses of 0, 0.3, 0.65, or 1 g/kg and subjected to the following: terminated at 45 min or 4 h post dosing, and blood and brain toluene concentration were measured; terminated at 4 h post dosing, and biomarkers of cardiac function were measured; or monitor heart rate (HR), core temperature (Tc), and motor activity (MA) by radiotelemetry before and after dosing. Brain toluene concentration was significantly elevated in aged rats at 4 h after dosing with either 0.3 or 1 g/kg. Blood toluene concentrations were unaffected by age. There were various interactions between aging and toluene-induced effects on cardiac biomarkers. Most notably, toluene exposure led to reductions in mRNA markers for oxidative stress in aged but not younger animals. Toluene also produced a reduction in cardiac endothelin-1 in aged rats. Higher doses of toluene led to tachycardia, hypothermia, and a transient elevation in MA. Aged rats were less sensitive to the tachycardic effects of toluene but showed a prolonged hypothermic response. Elevated brain levels of toluene in aged rats may be attributed to their suppressed cardiovascular and respiratory responses. The expression of several cardiac biochemical markers of toluene exposure in the aged may also reflect differential susceptibility to this toxicant.

The cardiovascular and thermoregulatory systems are considered to be susceptible in the aged population, but little is known about baseline cardiac and thermoregulatory homeostasis in rodent models of aging. Radiotransmitters were implanted in male, Brown Norway rats obtained at 4, 12, and 24 months to monitor the electrocardiogram (ECG), interbeat interval (IBI), heart rate (HR), core temperature (Tc), and motor activity (MA). There was no significant effect of age on resting HR and MA. Daytime Tc of the 24-month-old rats was significantly elevated above those of the 4- and 12-month-old groups. Variability of the IBI was highest in the 24-month-old rats. The elevation in daytime Tc beginning around 8 months of age may be a physiological biomarker of aging and may be an important factor to consider in studies using caloric restriction-induced hypothermia to increase longevity.

Ciguatoxins (CTX) are a suite of cyclic polyether toxins produced by the marine dinoflagellate Gambierdiscus sp., are potent activators of voltage-gated sodium channels and a leading cause of human poisoning from food fish. This report characterizes the genomic and proteomic response in whole blood of adult male mice exposed i.p. to 264 ng/kg of the Pacific congener of CTX (P-CTX-1) at 1, 4 and 24h. Whole genome microarray expression data were filtered by tightness of fit between replicates, fold change (1.8) and p-value (10(-5)), resulting in 183 annotated genes used for trending analysis, K-means clustering and ontology classification. Genes involved with cytokine signaling, proteasome complex and ribosomal function were dominant. qPCR performed on 19 genes of interest had a correlation of 0.95 to array results by Pearson's correlation coefficient. Serum protein analysis showed small but significant changes in 6 of 60 proteins assayed: Ccl2, Ccl12, CD40, IL-10, leptin and M-CSF. In large part, the gene expression was consistent with a Th2 immune response with interesting similarities to expression seen in asthmatic models.

Organophosphate (OP) and carbamate (CB) insecticides inhibit cholinesterase (ChE) activity and induce acute hypothermia in adult rats. Studies showed that juveniles are generally more susceptible to neurotoxic insult than adults. However, little is known concerning the effects of OP and CB pesticides on thermoregulation in developing animals. Thus, alterations in core body temperature (Tc) in juvenile animals exposed to an OP and CB insecticide were investigated. Male rat pups were anesthetized on postnatal day (PND) 15 with metofane and a radio transmitter (Data Sciences) was implanted in the abdominal cavity to monitor Tc and motor activity (MA). Two days were allowed for recovery. The PND 17 pups were then dosed by oral gavage with the OP chlorpyrifos (CHP) (1, 5, 10, or 15 mg/kg) or the CB carbaryl (CAR) (10, 20, 80, 120, or 160 mg/kg) or the corn oil vehicle. Pups were returned to their dams and littermates immediately after dosing and monitored for the next several days. CHP doses of 10 and 15 mg/kg resulted in 1.0 degrees C and 2.4 degrees C reductions in Tc, respectively. Tc recovered to control levels by approximately 16 h after dosing. There was significant mortality in rats dosed with 15 mg/kg CHP (6 of 11). CAR doses of 10 to 80 mg/kg had little effect on Tc. The highest dose of CAR (160 mg/kg) resulted in a 1.3 degrees C reduction in Tc that recovered in 9 h. In contrast, past studies found that adult male rats become hypothermic at CHP doses of >25 mg/kg, whereas a CAR dose of 50 mg/kg is effective at inducing hypothermia. Overall, it appears that during the development from preweanling to adult rat, there is a progressive attenuation in CHP-induced hypothermia. Conversely, CAR-induced hypothermia increases as a function of development.

This paper reports findings from the first phase of a national study conducted to identify the intention of nursing students' to work in a Primary Health Care setting following registration. An online survey of final year nursing students enrolled at Australian universities offering education leading to eligibility for registration as a nurse with the Australian Health Practitioner Regulation Agency was undertaken during July-August 2014. Data were collected about students' intention to enter Primary Health Care as a career option, as well as their exposure to primary health care during their nursing education and whether they had undertaken practice placements in a primary health care setting. Analysis was conducted on 456 completed surveys. The findings demonstrated that, despite the majority (98.2%; n = 447) of students being exposed to Primary Health Care during their studies, less than a quarter (22.8%; n = 104) of the students who responded identified this as an area in which they intended to work following registration. No association was found between students' clinical experiences and their identification of primary health care as a career preference. Given the ageing population in Australia, the increased prevalence of chronic health issues and the predicted ongoing primary health care workforce shortages, educational and workplace strategies aimed at attracting new graduate nurse into Primary Health Care settings are imperative.

The potential use of hypothermia as a therapeutic treatment for stroke and other pathological insults has prompted the search for drugs that can lower core temperature. Ideally, a drug is needed that reduces the set-point for control of core temperature (T(c)) and thereby induces a regulated reduction in T(c). To this end, a neurotensin analog (NT77) that crosses the blood brain barrier and induces hypothermia was assessed for its effects on the set-point for temperature regulation in the Sprague-Dawley rat by measuring behavioral and autonomic thermoregulatory responses. Following surgical implanation of radiotransmitters to monitor T(c), rats were placed in a temperature gradient and allowed to select from a range of ambient temperatures (T(a)) while T(c) was monitored by radiotelemetry. There was an abrupt decrease in selected T(a) from 29 to 16 degrees C and a concomitant reduction in T(c) from 37.4 to 34.0 degrees C 1 hr after IP injection of 5.0 mg/kg NT77. Selected T(a) and T(c) then recovered to control levels by 1.5 hr and 4 hr, respectively. Oxygen consumption (M) and heat loss (H) were measured in telemetered rats housed in a direct calorimeter maintained at a T(a) of 23.5 degrees C. Injection of NT77 initially led to a reduction in M, little change in H, and marked decrease in T(c). H initially rose but decreased around the time of the maximal decrease in T(c). Overall, NT77 appears to induce a regulated hypothermic response because the decrease in T(c) was preceded by a reduction in heat production, no change in heat loss, and preference for cold T(a)'s. Inducing a regulated hypothermic response with drugs such as NT77 may be an important therapy for ischemic disease and other insults.

Diazinon is an organophosphate (OP)-based, anticholinesterase insecticide that irreversibly inhibits acetylcholinesterase activity and produces cholinergic stimulation in central nervous system (CNS) and peripheral tissues. Our laboratory has found that OPs administered orally in rats induce a transient period of hypothermia followed by a delayed fever that persists for several days after exposure. There is little information on the thermoregulatory effects of diazinon. Core temperature (Tc) and motor activity (MA) were monitored by radiotelemetry in male and female rats of the Long-Evans strain dosed orally with diazinon (0 [corn-oil vehicle], 100, 200, or 300 mg/kg in males and 0, 50, 100, or 200 mg/kg in females). There was a dose-dependent decrease in Tc during the first night after treatment, with females exhibiting slightly greater sensitivity than males. MA was unaffected in females exposed to diazinon at doses of 50 to 200 mg/kg; MA of males was reduced during the first night after dosing with 300 mg/kg. There was a delayed elevation in Tc of males dosed with 200 and 300 mg/kg and females dosed with 50, 100, and 200 mg/kg diazinon. The elevated Tc was only manifested during d 2 and 3 after diazinon. Administration of 200 mg/kg sodium salicylate to females 48 h after being treated with 200 mg/kg diazinon led to a rapid abatement of the fever. Diazinon doses of 50 to 300 mg/kg led to 40% to 50% inhibition in plasma cholinesterase (ChE) activity 4 h after dosing, and females displayed a significantly slower recovery of ChE activity compared to males. When compared on a molar basis, the hypothermic response to diazinon was relatively small compared to other OPs such as chlorpyrifos. The delayed fever and efficacy of sodium salicylate to block diazinon-induced fever are similar to the effects of OPs chlorpyrifos and diisopropyl fluoro-phosphate (DFP).

Time of day of exposure is rarely considered in the study of insecticide toxicology. It would be expected that the circadian temperature rhythm (CTR) as well as the circadian rhythms of other physiological processes would affect the efficacy of anticholinesterase (antiChE) insecticides. The ability of antiChE insecticides to alter core temperature ( T c ) could be affected by time of exposure in relation to the CTR. To this end, we assessed time of exposure on the efficacy of the antiChE insecticides chlorpyrifos (CHP) and carbaryl (CAR) to alter T c in the rat. T c and motor activity (MA) were monitored by radiotelemetry. Rats were dosed orally with 0, 30, and 50 mg/kg CHP or 0, 25 and 75 mg/kg CAR at 09:00 and 15:00 h. Both insecticides caused an acute decrease followed by a delayed increase in T c by 24–48 h post-exposure. The temperature index (TI) (area under curve of Δ T c with time) was significantly greater when CHP was given at 15:00 h as compared with 09:00 h. The maximum decrease in T c was similar for morning and afternoon CHP. The TI following CAR was similar for morning and afternoon exposure. CHP suppressed the 24 h MA equally when given in the morning and afternoon. CAR was more effective in reducing MA when given in the morning as compared with the afternoon. The T c increase measured 24 h after dosing was greater when CHP was given in the morning. Overall, time of day affected the thermoregulatory toxicity of CHP but not CAR. Another experiment showed that the hypothermic efficacy of oxotremorine, a muscarinic agonist, was greater when injected at 09:00 h as compared with 15:00 h. Hence, cholinergic stimulation is probably not the only mechanism to explain the effects of the chronotoxicogical effects of some antiChE insecticides.

Our laboratory has found that the organophosphate pesticide chlorpyrifos elicits an elevation in blood pressure that persists for approximately 24 hr after exposure. Since organophosphate pesticides inhibit acetylcholinesterase activity and cause cholinergic stimulation in the central nervous system and peripheral tissues, we suspect that the hypertensive response from chlorpyrifos is elicited by activation of pressor areas in the brain stem, specifically muscarinic receptors which are known to mediate hypertensive responses. Oxotremorine, a muscarinic agonist, should elicit a blood pressure response similar to organophosphate pesticides. This study used radiotelemetry to assess the effects of oxotremorine on blood pressure, heart rate, core temperature, QA interval (a measure of cardiac contractility), and motor activity in the male, Long-Evans rat. Subcutaneous co-administration of 0.2 mg/kg oxotremorine with 1.0 mg/kg methyl scopolamine (i.e., to block oxotremorine's peripheral effects) caused a marked elevation in blood pressure that developed concomitantly with a 2 degrees decrease in core temperature, 60 beats/min. increase in heart rate, increase in cardiac contractility but no change in motor activity. Overall, blood pressure increased by 19 mmHg from baseline and the response persisted for approximately 12 hr after injection. Methyl scopolamine alone increased heart rate but had no effect on blood pressure, core temperature, and motor activity. Oxotremorine injected without methyl scopolamine led to a relatively minor increase in blood pressure and hypothermia. Overall, central muscarinic stimulation with oxotremorine and methyl scopolamine leads to a vigorous hypertensive response that is associated with increased cardiac contractility, suggesting an increase in cardiac output. Combined central and peripheral cholinergic stimulation following oxotremorine without methyl scopolamine, as would also occur with exposure to chlorpyrifos and other organophosphate pesticides, did not elicit as much of a hypertensive response. This would suggest pathways other than those controlled directly with muscarinic receptors are operative in the development of chlorpyrifos-induced hypertension.

Mastery of auscultatory blood pressure is challenging for preregistration nursing students. This phenomenon has been attributed to the psychomotor skills required, knowledge about blood pressure measurement, and the teaching modality type. Most studies focus on developing blood pressure proficiency without determining the measurement accuracy. We sought to determine the efficacy of simulation-based learning on blood pressure measurement accuracy in first-year preregistration nursing students.First-year preregistration nursing students from a clinical subject were randomly assigned to laboratory groups, which formed the control and intervention groups. Each group received identical blood pressure measurement education, with the intervention group undertaking 2 additional hours of tuition, using human patient simulators programmed with a wide range of blood pressure measurements to replicate patient's blood pressures observed in clinical settings. At the end of the semester and after 40 hours of hospital clinical practice, participants were assessed for blood pressure accuracy on live subjects and completed a questionnaire on self-ratings of confidence and technical ability.Blood pressure accuracy was not significantly different between participants and assessors or between the control and intervention groups (all P0.05). The intervention group reported greater levels of confidence (P = 0.02) and self-rated technical ability (P = 0.01) in blood pressure measurement at week 14 of the semester; however, these difference were not observed at the end of 40 hours of clinical practice (P0.05).Accuracy in taking blood pressure was not enhanced by the use of a patient simulator, despite improvements in self-reported confidence and technical competency. Further research is required to evaluate the inclusion of simulation-based learning for blood pressure training in nursing students.

Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α2-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2> 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation.

Nicotine elicits hypothermic responses in rodents. This effect appears to be related to nicotinic receptor desensitization because sazetidine-A, an α4β2 nicotinic receptor desensitizing agent, produces marked hypothermia and potentiates nicotine-induced hypothermia in mice. To determine the specificity of sazetidine-A induced hypothermia to β2 subunit-containing nicotinic receptors, we tested its efficacy in β2 knockout (β2 −/− ) mice. These effects were compared with wildtype (WT) and α7 knockout (α7 −/− ) mice. Confirming our earlier results, sazetidine-A elicited a pronounced and long-lasting hypothermia in WT mice. In comparison, sazetidine-A induced a much attenuated and shorter hypothermic response in β2 −/− mice. This indicates that the greater proportion of sazetidine-A induced hypothermia is mediated via actions on β2-containing nicotinic receptors, while a smaller component of hypothermia induced by sazetidine-A is mediated by non-β2 receptors. Similar to WT mice, α7 −/− mice showed the full extent of the sazetidine-A effect, suggesting that the hypothermia produced by sazetidine-A did not depend on actions on α7 nicotinic receptor subtype. Three other novel nicotinic receptor desensitizing agents derived from sazetidine-A, triazetidine-O, VMY-2-95 and YL-1-127 also produced hypothermia in WT and α7 −/− mice. Furthermore, unlike sazetidine-A, triazetidine-O and YL-1-127 did not show any hint of a hypothermic effect in β2 −/− mice. VMY-2-95 like sazetidine-A did show a residual hypothermic effect in the β2 −/− mice. These studies show that the hypothermic effects of sazetidine-A and the related compound VMY-2-95 are mainly mediated by nicotinic receptors containing β2 subunit, but that a small component of the effect is apparently mediated by non-β2 containing receptors.

Ozone (O₃) is a pervasive air pollutant that produces pulmonary and cardiovascular dysfunction and possible neurological dysfunction. Young and old individuals are recognized as being susceptible to O₃; however, remarkably little is known about susceptibility with senescence. This study explored the pulmonary, cardiovascular and neurological effects of O₃ exposure in adult (4 m) and senescent (20 m) Brown Norway rats exposed to 0 or 0.8 ppm O₃ for 6 h, 1 d/week, for 17 weeks. Ventilatory function was assessed 1 and 7 d after each exposure (Buxco). Heart rate, blood pressure (tail cuff) and motor activity were measured biweekly. Blood, aorta and bronchoalveolar lavage fluid (BALF) were analyzed 24 h after the last exposure for pulmonary inflammation, serum biomarkers and aorta mRNA markers of vascular disease. Measures of normal ventilatory function declined following each O₃ exposure in both adult and senescent rats, however, senescent rats took weeks to exhibit a decline. Evidence for residual respiratory effects of O₃ 7 d after exposure in both age groups was observed. O₃ had no effect on either heart rate or blood pressure, but decreased motor activity in both age groups. BALF indicated mild neutrophilic inflammation and protein leakage in adults. Age affected 17/58 serum analytes, O₃ affected 6/58; 2/58 showed an age-O₃ interaction. Leptin, adiponectin, lipocalin and insulin were increased in senescent rats. Overall, adult rats exhibited more immediate effects of episodic O₃ than senescent rats. Residual effects were, however, obtained in both ages of rat, especially for ventilatory endpoints.