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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.

The laboratory mouse has become the predominant test species in biomedical research. The number of papers that translate or extrapolate data from mouse to human has grown exponentially since the year 2000. There are many physiological and anatomical factors to consider in the process of extrapolating data from one species to another. Body temperature is, of course, a critical determinant in extrapolation because it has a direct impact on metabolism, cardiovascular function, drug efficacy, pharmacokinetics of toxins and drugs, and many other effects. While most would consider the thermoregulatory system of mice to be sufficiently stable and predictable as to not be a cause for concern, the thermal physiology of mice does in fact present unique challenges to the biomedical researcher. A variable and unstable core temperature, high metabolic rate, preference for warm temperatures, large surface area: body mass ratio, and high rate of thermal conductance, are some of the key factors of mice that can affect the interpretation and translation of data to humans. It is the intent of this brief review to enlighten researchers studying interspecies translation of biomedical data on the salient facets of the mouse thermal physiology and show how extrapolation in fields such as physiology, psychology, nutrition, pharmacology, toxicology, and pathology.

Laboratories and vivariums typically are maintained at ambient temperatures of 20 to 24 °C, leading to cold stress in mice. When mice are inactive and sleeping during the light phase, their zone of thermoneutrality associated with a basal metabolic rate is 30 to 32 °C. If given a choice, mice will use thermoregulatory behavior to seek out thermoneutral temperatures during the light phase. The cold stress of a vivarium can be problematic to researchers requiring an animal model that is not stressed metabolically. However, it may not be practical or economically feasible to maintain an animal vivarium at thermoneutral temperatures. One problem with raising the ambient temperature of a vivarium is that personnel wearing protective equipment will be subject to considerable heat stress. Here we present plans for the construction and operation of a device that allows mice to access a heated floor that is maintained at an approximate thermoneutral temperatures (30 to 32 °C). The device is made of inexpensive, readily available materials and uses a disposable hand warmer as a heat source. One hand warmer provides a thermoneutral environment for approximately 12 h. This device is easily adapted to a standard mouse or rat cage and requires only brief daily maintenance to change the heating pad. With this device in a standard cage, mice can select a warmer environment associated with thermoneutral conditions during the light phase and cooler ambient temperatures during the dark phase.

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.

We show here that fundamental aspects of antitumor immunity in mice are significantly influenced by ambient housing temperature. Standard housing temperature for laboratory mice in research facilities is mandated to be between 20-26 °C; however, these subthermoneutral temperatures cause mild chronic cold stress, activating thermogenesis to maintain normal body temperature. When stress is alleviated by housing at thermoneutral ambient temperature (30-31 °C), we observe a striking reduction in tumor formation, growth rate and metastasis. This improved control of tumor growth is dependent upon the adaptive immune system. We observe significantly increased numbers of antigen-specific CD8(+) T lymphocytes and CD8(+) T cells with an activated phenotype in the tumor microenvironment at thermoneutrality. At the same time there is a significant reduction in numbers of immunosuppressive MDSCs and regulatory T lymphocytes. Notably, in temperature preference studies, tumor-bearing mice select a higher ambient temperature than non-tumor-bearing mice, suggesting that tumor-bearing mice experience a greater degree of cold-stress. Overall, our data raise the hypothesis that suppression of antitumor immunity is an outcome of cold stress-induced thermogenesis. Therefore, the common approach of studying immunity against tumors in mice housed only at standard room temperature may be limiting our understanding of the full potential of the antitumor immune response.

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.

Purpose: Simulation in physiotherapy education is increasing, but a standardised assessment tool for student performance in simulation has not been developed. The Assessment of Physiotherapy Practice (APP) is a validated tool for student performance in the clinical workplace, and has been used recently for simulation despite its relevance for this context being unknown. The purpose of the study was to gain consensus about which APP items should be included in a tool to assess physiotherapy students’ performance in simulation. The relevance of items was considered for both single patient encounters, and longitudinal (multiple) encounters. Methods: An online Delphi approach used a custom designed survey. A purposive sample of physiotherapists with simulation experience was recruited via email. Two rounds were undertaken with consensus being reached when at least 80% of the panel agreed on inclusion or exclusion of an item. Results: Twenty participants responded in the first round and fourteen in the second (70% retention). For longitudinal simulations, all APP items reached consensus in the first round. For single patient simulation encounters, consensus was not reached in the first round for the following items: commitment to learning (61%), teamwork (76%) and discharge planning (72%). In the second round, consensus for ‘teamwork’ remained the only item below eighty percent agreement (78.6%). Conclusions: The APP was deemed to be an appropriate measure for longitudinal clinical simulations, and with the exclusion of teamwork, for a single patient simulation encounter.

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.

To explore new graduate registered nurses' reflections of bioscience courses during their nursing programme and the relationship between bioscience content and their clinical practice.Undergraduate nursing students internationally find bioscience courses challenging, which may be due to the volume of content and level of difficulty of these courses. Such challenges may be exacerbated by insufficient integration between bioscience theory and nursing clinical practice.A descriptive, cross-sectional mixed methods study was conducted.A 30-item questionnaire with five written response questions which explored recently registered nurses' reflections on bioscience courses during their nursing degree was employed. Descriptive analyses were reported for individual items. Thematic analysis of qualitative responses was grouped to reveal emerging themes.Registered nurses' (n = 22) reflections revealed that bioscience courses were a significant challenge during their undergraduate programme, and they lacked confidence explaining the biological basis of nursing. Participants would like improved knowledge of the relevant bioscience for nursing and agreed that bioscience courses should be extended into the undergraduate final year. The importance of relating bioscience content to nursing practice was elaborated extensively throughout written responses.Although registered nurses reflected that bioscience courses were difficult with large volumes of content, having more bioscience with greater relevance to nursing applications was considered important in their current clinical practice. It is suggested that bioscience academics develop greater contextual links between bioscience content and clinical practice relevant to nursing.After working as a registered nurse, there was appreciation of bioscience relevance for clinical practice, and the nurses believed they would have benefitted from more nursing-related bioscience during their undergraduate programme. Focussed integration of bioscience with clinical nursing courses should be driven by academics, nurse educators and clinical nurses to provide a biological basis for patient care to nursing students.

Background More and better interprofessional practice is predicated to be necessary to deliver good care to the patients of the future. However, universities struggle to create authentic learning activities that enable students to experience the dynamic interprofessional interactions common in healthcare and that can accommodate large interprofessional student cohorts. We investigated a large-scale mandatory interprofessional learning (IPL) activity for health professional students designed to promote social learning. Methods A mixed methods research approach determined feasibility, acceptability and the extent to which student IPL outcomes were met. We developed an IPL activity founded in complexity theory to prepare students for future practice by engaging them in a self-directed (self-organised) learning activity with a diverse team, whose assessable products would be emergent creations. Complicated but authentic clinical cases (n = 12) were developed to challenge student teams (n = 5 or 6). Assessment consisted of a written management plan (academically marked) and a five-minute video (peer marked) designed to assess creative collaboration as well as provide evidence of integrated collective knowledge; the cohesive patient-centred management plan. Results All students (including the disciplines of diagnostic radiology, exercise physiology, medicine, nursing, occupational therapy, pharmacy, physiotherapy and speech pathology), completed all tasks successfully. Of the 26 % of students who completed the evaluation survey, 70 % agreed or strongly agreed that the IPL activity was worthwhile, and 87 % agreed or strongly agreed that their case study was relevant. Thematic analysis found overarching themes of engagement and collaboration-in-action suggesting that the IPL activity enabled students to achieve the intended learning objectives. Students recognised the contribution of others and described negotiation, collaboration and creation of new collective knowledge after working together on the complicated patient case studies. The novel video assessment was challenging to many students and contextual issues limited engagement for some disciplines. Conclusions We demonstrated the feasibility and acceptability of a large scale IPL activity where design of cases, format and assessment tasks was founded in complexity theory. This theoretically based design enabled students to achieve complex IPL outcomes relevant to future practice. Future research could establish the psychometric properties of assessments of student performance in large-scale IPL events. Electronic supplementary material The online version of this article (doi:10.1186/s12909-016-0717-y) 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.

Background Previous research has demonstrated that digital CBT (dCBT), delivered via the Internet, is a scalable and effective intervention for treating insomnia in otherwise healthy adults and leads to significant improvements in primary outcomes relating to sleep. The majority of people with insomnia, however, seek help because of the functional impact and daytime consequences of poor sleep, not because of sleep discontinuity per se. Although some secondary analyses suggest that dCBT may have wider health benefits, no adequately powered study has investigated these as a primary endpoint. This study specifically aims to investigate the impact of dCBT for insomnia upon health and well-being, and will investigate sleep-related changes as mediating factors. Methods/design We propose a pragmatic, parallel-group, randomised controlled trial of 1000 community participants meeting criteria for insomnia disorder. In the DIALS trial (Digital Insomnia therapy to Assist your Life as well as your Sleep), participants will be randomised to dCBT delivered using web and/or mobile channels (in addition to treatment as usual (TAU)) or to sleep hygiene education (SHE), comprising a website plus a downloadable booklet (in addition to TAU). Online assessments will take place at 0 (baseline), 4 (mid-treatment), 8 (post-treatment), and 24 (follow-up) weeks. At week 25 all participants allocated to SHE will be offered dCBT, at which point the controlled element of the trial will be complete. Naturalistic follow-up will be invited at weeks 36 and 48. Primary outcomes are functional health and well-being at 8 weeks. Secondary outcomes are mood, fatigue, sleepiness, cognitive function, productivity and social functioning. All main analyses will be carried out at the end of the final controlled follow-up assessments and will be based on the intention-to-treat principle. Further analyses will determine whether observed changes in functional health and well-being are mediated by changes in sleep. The trial is funded by Big Health Ltd. Discussion This study will be the first large-scale, specifically designed investigation of the health and well-being benefits of CBT for insomnia, and the first examination of the association between CBT-mediated sleep improvement and health status. Trial registration ISRCTN60530898. Electronic supplementary material The online version of this article (doi:10.1186/s13063-016-1364-7) contains supplementary material, which is available to authorized users.

Background Increases in ageing, chronic illness and complex co-morbidities in the Australian population are adding pressure to the primary care nursing workforce. Initiatives to attract and retain nurses are needed to establish a sustainable and skilled future primary care nursing workforce. We implemented a transition to professional practice program in general practice settings for graduate nurses and evaluated graduate nurse competency, the graduate nurse experience and program satisfaction. This study aimed to determine whether a transition to professional practice program implemented in the general practice setting led to competent practice nurses in their first year post-graduation. Methods A longitudinal, exploratory mixed-methods design was used to assess the pilot study. Data were collected at three times points (3, 6, 12 months) with complete data sets from graduate nurses (n = 4) and preceptors (n = 7). We assessed perceptions of the graduates’ nursing competency and confidence, satisfaction with the preceptor/graduate relationship, and experiences and satisfaction with the program. Graduate nurse competency was assessed using the National Competency Standards for Nurses in General Practice. Semi-structured interviews with participants at Time 3 sought information about barriers, enablers, and the perceived impact of the program. Results Graduate nurses were found to be competent within their first year of clinical practice. Program perceptions from graduate nurses and preceptors were positive and the relationship between the graduate nurse and preceptor was key to this development. Conclusions With appropriate support registered nurses can transition directly into primary care and are competent in their first year post-graduation. While wider implementation and research is needed, findings from this study demonstrate the potential value of transition to professional practice programs within primary care as a nursing workforce development strategy.

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.

Heart rate variability (HRV) is an objective marker that provides insight into autonomic nervous system dynamics. There is conflicting evidence regarding the presence of HRV impairment in insomnia patients. Web-based databases were used to systematically search the literature for all studies that compared the HRV of insomnia patients to controls or reported the HRV of insomnia patients before and after an intervention. 22 relevant papers were identified. Study characteristics were summarised, HRV measures were extracted and a risk of bias assessment for each study was performed. We were limited in our ability to synthesise outcome measures and perform meta-analyses due to considerable differences in patient (and control) selection, study protocols, measurement and processing techniques and outcome reporting. Risk of bias was deemed to be high in the majority of studies. As such, we cannot confirm that HRV is reliably impaired in insomnia patients nor determine the HRV response to interventions. Whilst HRV impairment in insomnia is a widely accepted concept, it is not supported by empirical evidence. Large longitudinal studies incorporating 24-hour recordings are required to elucidate the precise nature of HRV dynamics in insomnia patients.

Introduction The use of simulation in health professional education has increased rapidly over the past 2 decades. While simulation has predominantly been used to train health professionals and students for a variety of clinically related situations, there is an increasing trend to use simulation as an assessment tool, especially for the development of technical-based skills required during clinical practice. However, there is a lack of evidence about the effectiveness of using simulation for the assessment of competency. Therefore, the aim of this systematic review was to examine simulation as an assessment tool of technical skills across health professional education. Methods A systematic review of Cumulative Index to Nursing and Allied Health Literature (CINAHL), Education Resources Information Center (ERIC), Medical Literature Analysis and Retrieval System Online (Medline), and Web of Science databases was used to identify research studies published in English between 2000 and 2015 reporting on measures of validity, reliability, or feasibility of simulation as an assessment tool. The McMasters Critical Review for quantitative studies was used to determine methodological value on all full-text reviewed articles. Simulation techniques using human patient simulators, standardized patients, task trainers, and virtual reality were included. Results A total of 1,064 articles were identified using search criteria, and 67 full-text articles were screened for eligibility. Twenty-one articles were included in the final review. The findings indicated that simulation was more robust when used as an assessment in combination with other assessment tools and when more than one simulation scenario was used. Limitations of the research papers included small participant numbers, poor methodological quality, and predominance of studies from medicine, which preclude any definite conclusions. Conclusion Simulation has now been embedded across a range of health professional education and it appears that simulation-based assessments can be used effectively. However, the effectiveness as a stand-alone assessment tool requires further research.

Epidemiological data suggest that a sedentary lifestyle may contribute to increased susceptibility for some environmental toxicants. We developed an animal model of active versus sedentary life style by providing female Sprague-Dawley rats with continuous access to running wheels. Sedentary rats were housed in standard cages without wheels. After training for 12 wks, rats were exposed to 0, 0.25, 0.5 or 1.0ppm ozone [O-3 for 5 h/d, 1 d/wk, for 6 wk (N = 10 per group)]. Body composition (%fat, lean and fluid) was monitored noninvasively over the course of the study. Ventilatory parameters [tidal volume, minute ventilation, frequency and enhanced pause (Penh)] were assessed using whole-body plethysmography prior to O-3 and 24 h after the 5th O-3 exposure. Trained rats lost similar to 2% body fat after 12 wk of access to running wheels. Peak wheel activity was reduced by 40% after exposure to 1.0ppm O-3. After the 5th O-3 exposure, body weight and % fat were reduced in sedentary but not trained rats. Penh was significantly elevated in sedentary but not trained rats the day after exposure to 1.0 ppm O-3. However, lung lavage cell counts and biomarkers of pulmonary inflammation measured 1 day after the final exposure were inconsistently affected by training. Wheel running led to marked physiological responses along with some indication of improved pulmonary recovery from O-3 exposure. However, wheel running with O-3 exposure may also be a detriment for some pulmonary endpoints. Overall, a sedentary lifestyle may increase susceptibility to O-3, but additional studies are needed.

In terms of total number of publications, the laboratory mouse (Mus musculus) has emerged as the most popular test subject in biomedical research. Mice are used as models to study obesity, diabetes, CNS diseases and variety of other pathologies. Mice are classified as homeotherms and regulate their core temperature over a relatively wide range of ambient temperatures. However, researchers find that the thermoregulatory system of mice is easily affected by drugs, chemicals, and a variety of pathological conditions, effects that can be exacerbated by changes in ambient temperature. To this end, a thorough review of the thermal physiology of mice, including their sensitivity and regulatory limits to changes in ambient temperature is the primary focus of this review. Specifically, the zone of thermoneutrality for metabolic rate and how it corresponds to that for growth, reproduction, development, thermal comfort, and many other variables is covered. A key point of the review is to show that behavioral thermoregulation of mice is geared to minimize energy expenditure. Their zone of thermal comfort is essentially wedged between the thresholds to increase heat production and heat loss; however, this zone is above the recommended guidelines for animal vivariums. Future work is needed to better understand the behavioral and autonomic thermoregulatory responses of this most popular test species.

A feasibility study was performed to compare an investigational drug, HBN-1, to forced cooling to induce hypothermia after resuscitation in a translation model of asphyxial cardiac arrest in swine. Serum and cerebral spinal fluid neuron-specific enolase activity (sNSE and csfNSE) were measured after cardiac arrest as surrogate markers of brain injury. In a block design, swine resuscitated from 10 minutes of asphyxial cardiac arrest were infused intravenously with HBN-1 or iced saline vehicle (forced hypothermia [FH]) 5 to 45 minutes after return of spontaneous circulation (ROSC). External cooling in both groups was added 45 minutes after ROSC until hypothermia (T=4°C below baseline) was attained. Esophageal (core) temperature, shivering, cardiopulmonary parameters, and time to hypothermia after ROSC were monitored. sNSE and csfNSE were measured 180 minutes after ROSC. HBN-1 induced hypothermia significantly lowered temperature compared to FH 5-45 minutes after ROSC (p

Mice, rats, and nearly all mammals and birds are classified as homeothermic, meaning that their core temperature is regulated at a constant level over a relatively wide range of ambient temperatures. In one sense, this homeothermic designation has been confirmed by the advent of radiotelemetry and other techniques that allow for the remote monitoring of awake, unrestrained animals in laboratory or natural settings. This technology confirmed that, when averaged over many hours, core temperature of mammals is regulated at a nearly constant level. On the other hand, telemetric sampling in relatively small mammals such as mice and rats also revealed that their core temperature often varies markedly from hour to hour. In other words, the mouse could be defined as a homeotherm only when core temperature is averaged over a relatively long period. Many researchers ascribe equal homeothermic capabilities to mice and other small rodents as they do to humans. Such an assumption could lead to errors in extrapolating physiological, pharmacological, and toxicological findings from experimental test species to humans.

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.

Physical restraint of rodents is needed for nose-only exposure to airborne toxicants and is also used as a means of psychological stress. Hyperthermia is often observed in restrained rats, presumably as a result of impairments in heat dissipation. However, such a hyperthermic response should be dependent on the prevailing ambient conditions. To understand how ambient temperature (T(a)) affects the thermoregulatory response to restraint, core temperature (T(c)) and heart rate (HR) were monitored by telemetry in rats subjected to 1 h of physical restraint while T(a) was maintained at 14-30 °C in 2 °C increments. The T(c) of unrestrained rats was unaffected by T(a). During restraint, T(c) was elevated at ambient temperatures with the exception of 14 °C, at which the rats became mildly hypothermic. There was an inverse relationship between T(a) and HR in both unrestrained and restrained rats; however, HR was significantly elevated in restrained rats at all ambient temperatures except 22 and 24 °C. Heat loss from the tail, estimated from T(c) and tail skin temperature, was markedly reduced at all but the highest ambient temperatures in restrained rats. The data suggest that the T(a) limits of normothermia are narrowed in the restrained rat. That is, between 16 and 20 °C, the rat maintains a relatively stable T(c) that is slightly elevated above that of the unrestrained rat. At ambient temperatures above or below this range, the rat shows signs of hyperthermia and hypothermia, respectively. In contrast, the limits of normothermia for unrestrained rats range from 14 (or lower) to 30 °C. Overall, the ideal T(a) for restrained rats appears to be 20 °C and no higher than 22 °C for the thermoregulatory system to maintain a regulated T(c) in rats well adapted to physical restraint.

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.

Patient: 55-year-old Hispanic male Chief Complaint: Three weeks pre-mortem: pleuritic chest pain, shortness of breath, and fatigue. History of Present Illness: The patient presented for routine monitoring of his heart transplant and complained of body weakness and positional chest discomfort. An echocardiogram showed a large pericardial effusion. A pericardiocentesis was performed and 550 mL of serosanguinous fluid was removed. Following pericardiocentesis, his symptoms improved temporarily. His condition worsened over the next 3 weeks, and he died. Past Medical History: Ischemic cardiomyopathy treated with a heart transplant 1 month prior to hospitalization, type II diabetes mellitus, hypertension, hyperlipidemia, severe gastritis, and status-post cholecystectomy. He was currently taking tacrolimus, mycophenolate mofetil, and prednisone to prevent rejection of his heart allograft. At presentation, a level of tacrolimus measured at its trough was supratherapeutic. Family History: The patient’s father and brother have a history of coronary artery disease. Social History: The patient is an ex-smoker, who quit 20 years ago (10 pack years). He denies alcohol and illicit drug use. He was a landscaper until the month before his heart transplant. Autopsy Findings: 1. Solid white embolus filling the left anterior descending coronary artery. There were multifocal white areas consistent with acute ischemia, most notable in the distribution of this artery (Image 3A and Image 3B). Multiple sections of myocardium at autopsy showed no change in his grade of cellular rejection, and confirmed the absence of humoral rejection. 2. The pleural surfaces of the lungs show multi-focal fibrous patches consistent with adhesions (Image 3C). The lungs were diffusely congested, and the tracheobronchial tree was free of obstructions. There were bilateral serosanguinous effusions, totaling more than 2 liters. 3. Bile-stained liver (1300 g) with centrilobular necrosis and perisinusoidal fibrosis. Laboratory and Pathology Findings: A number of abnormal laboratory values were identified 1 day premortem (Table 1). A cardiac …

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.

Radiotelemetry provides researchers with the ability to sample the core temperature of rodents and other species rapidly. Compared to large mammals, the time-course of core temperature of rodents is variable and their data are often averaged into bins of one or more hours for publication. When viewing averaged data, a stable core temperature over a wide range of ambient temperatures is observed; however, if the time-course of core temperature of individual animals is examined closely with a sampling period of 1–10 min, a continuous waxing and waning of temperature is observed. It is proposed that calculating the change in temperature from one time point to the next (i.e., temperature differential) is an informative measure of the performance of the thermoregulatory system. A quantitative measure of the stability of the thermoregulatory system can be determined by calculating the absolute value of the temperature differential. It is shown that the absolute temperature differential (ATD) is dependent on ambient temperature, genetic strain, type of cage bedding, and body size. The ATD is simple to calculate from telemetry data and may be an important parameter for the study of rodent thermal physiology.

Hypothermic preconditioning is rapid cooling and warming to induce tolerance to ischemia. The purpose of the study was to examine differences in brain and trunk temperature during hypothermic preconditioning.Rats (n=18) were implanted with telemetric probes for simultaneous measure of brain and trunk temperature. Hypothermic preconditioning was produced by exposing rats to cool and warm environments that produced rapid cooling to 30 degrees C and warming to 35 degrees C.Brain temperature was warmer (37.56+/-0.45 degrees C) than trunk (37.17+/-0.29 degrees C) temperature in unanesthetized, free roaming rats at room temperature (t-test p=0.04). The brain cooled (0.59+/-0.1 degrees C/min) quicker than the trunk (0.44+/-0.19 degrees C/min) during cooling cycles of hypothermic preconditioning and the brain (0.28+/-0.04 degrees C/min) warmed quicker than the trunk (0.18+/-0.07 degrees C/min) during the warming cycle of hypothermic preconditioning (t-test p0.0001). When the trunk temperature probe was designated to reach the target temperature of 35 degrees C during warming, the brain temperature (38.1+/-0.44 degrees C) was warmer than trunk temperature (34.95+/-0.16 degrees C) during the peak of warming (t-test p0.0001).The brain cools and warms quicker than the trunk during hypothermic preconditioning. Failure to anticipate these differences could lead to unrecognized brain hyperthermia during warming. Appreciation of differences in rates of change between brain and trunk temperature may be important when designing hypothermic preconditioning experiments.

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.

Nursing students have reported bioscience to be challenging and difficult to understand. This might have a negative impact upon their ability to understand patients' clinical conditions and nursing practice. We sought information about students' experiences with bioscience. A total of 126 final year nursing students completed a questionnaire. The findings showed that the majority of participants considered bioscience subjects to require more work compared to nursing subjects (65.9%), and that they would like a better understanding of bioscience (73.8%), but understood that bioscience forms the foundation of nursing practice (76.2%). Younger participants without secondary school science rated bioscience harder than nursing subjects and spent more time studying bioscience compared to older participants. Participants without any secondary school science lacked an ability to apply bioscience concepts to patient conditions. These results showed that nursing students, especially those without secondary school science, would benefit from improved bioscience integration with nursing practice. Nursing and bioscience educators should consider greater alignment of bioscience with nursing practice subjects, especially earlier in the curriculum.

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.

1. To avoid anesthesia confounders, free-ranging rats were exposed (4 h) to cool water (CW; 10 °C; 5 cm), warm water (WW; 35 °C; 5 cm) or temperate air (TA; 25 °C) to induce hypothermia, or control for water or novel environment stress, respectively. 2. While WW and TA core temperature (Tc) and the brown adipose tissue (TBAT)/subdermal skin (TSDS) temperature relationship remained similar, CW hypothermia induction was variable (34.5–26.1 °C; 9–240 min) and associated with tachycardia (517.8±4.7 bpm) greater than WW (386.5±5.5 bpm) or TA (372.2±7.7 bpm) with CW TBAT (36.5±0.03 °C) elevated above CW TSDS (35.9±0.05 °C). 3. Without anesthesia to blunt thermoregulatory countermeasures to hypothermia, variable resistance to Tc depression, tachycardia rather than bradycardia and BAT thermogenic responses were demonstrated.

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.

Bioscience content within undergraduate nursing degrees provides foundational knowledge of pathophysiology, anatomy, physiology, microbiology and pharmacology. However, nursing students often find studying the bioscience components of undergraduate nursing program daunting (Friedel & Treagust 2005, Craft et al. 2013). This is related to factors such as the volume of content, degree of difficulty and insufficient linkage between bioscience concepts and nurses' clinical practice. Students who are unable to conceptualise the relevance of bioscience with nursing subjects and subsequent nursing practice may not appreciate the broader importance of bioscience, and hence may adopt a surface approach to learning (Craft et al. 2013). The aim of this study was to develop a model within Nursing Practice in the Context theory subject, to include a bioscientist lecturing to complement the nursing lecturer, in order to explicitly demonstrate links between physiology, pathophysiology and nursing practice.