Mathematical Analysis of Light-sensitivity Related Challenges in Assessment of the Intrinsic Period of the Human Circadian Pacemaker.

Accurate assessment of the intrinsic period of the human circadian pacemaker is essential for a quantitative understanding of how our circadian rhythms are synchronized to exposure to natural and man-made light-dark (LD) cycles. The gold standard method for assessing intrinsic period in humans is forced desynchrony (FD) which assumes that the confounding effect of lights-on assessment of intrinsic period is removed by scheduling sleep-wake and associated dim LD cycles to periods outside the range of entrainment of the circadian pacemaker. However, the observation that the mean period of free-running blind people is longer than the mean period of sighted people assessed by FD (24.50 ± 0.17 h vs 24.15 ± 0.20 h, p <0.001) appears inconsistent with this assertion. Here, we present a mathematical analysis using a simple parametric model of the circadian pacemaker with a sinusoidal velocity response curve (VRC) describing the effect of light on the speed of the oscillator. The analysis shows that the shorter period in FD may be explained by exquisite sensitivity of the human circadian pacemaker to low light intensities and a VRC with a larger advance region than delay region. The main implication of this analysis, which generates new and testable predictions, is that current quantitative models for predicting how light exposure affects entrainment of the human circadian system may not accurately capture the effect of dim light. The mathematical analysis generates new predictions which can be tested in laboratory experiments. These findings have implications for managing healthy entrainment of human circadian clocks in societies with abundant access to light sources with powerful biological effects.

Inaccuracy of surgical irrigation fluid temperature hand assessment.

INTRODUCTION: Fluids are often used for irrigation during surgical procedures. The temperature of the fluid directly affects the exposed tissue and body temperature. The recommended practice is to use euthermic fluids to be homeostatic and optimise patient care. Hand checking the fluid temperature by surgeons and scrub practitioners is the commonly used method. This subjective measurement leaves room for error and can lead to inaccuracies. The purpose of the study is to assess the accuracy of the currently used method of checking irrigation fluids temperature by hand immersion. METHOD: Two sets of fluids were prepared. One was made at 37°C and the other was 30°C. Participants immersed their hands in the containers and then report if each of the two sets is (1) appropriately warm for irrigation, (2) too cool and (3) too warm. Data were collected and interpreted. RESULTS: Results showed that about half of participants in our study perceived normal physiologic fluid temperature as too hot for use in irrigation, 30°C fluid was perceived as appropriate and physiologic by about a quarter of participants. CONCLUSIONS: Perception of surgical irrigation fluid temperature by hand immersion is inaccurate. Standard objective methods of measuring the temperature are recommended.

Measurements of body temperature and oxidative stress reveal differential costs associated with humoral immune function in a passerine bird.

Eco-immunology considers resistance to antigens a costly trait for an organism, but actual quantification of such costs is not straightforward. Costs of the immune response are visible in impaired coloration and reduced growth or reproductive success. Activation of the humoral immune response is a slow, complex and long-lasting process, which makes the quantification of its energetic cost a potential losing game. We implemented near-continuous measurements of body temperature in zebra finches (Taeniopygia guttata) as a proxy for the energetic cost, with a particular focus during activation of the humoral immune response until the peak of antibody release several days later. At the peak of the antibody release we additionally measured oxygen consumption (open-flow respirometry) and markers of oxidative stress (dROMs, OXY). Birds with an activated immune response maintained a higher night-time body temperature during the first 4 nights after an immune challenge in comparison to controls, implying increased night-time energy use. At peak antibody production, we did not find differences in night-time body temperature and oxygen consumption but observed differentiated results for oxygen consumption during the day. Immune-challenged females had significantly higher oxygen consumption compared with other groups. Moreover, we found that activation of the humoral immune response increases oxidative damage, a potential cost of maintaining the higher night-time body temperature that is crucial at the early stage of the immune response. The costs generated by the immune system appear to consist of two components - energetic and non-energetic - and these appear to be separated in time.

Fevers and the social costs of acute infection in wild vervet monkeys.

Fevers are considered an adaptive response by the host to infection. For gregarious animals, however, fever and the associated sickness behaviors may signal a temporary loss of capacity, offering other group members competitive opportunities. We implanted wild vervet monkeys (Chlorocebus pygerythrus) with miniature data loggers to obtain continuous measurements of core body temperature. We detected 128 fevers in 43 monkeys, totaling 776 fever-days over a 6-year period. Fevers were characterized by a persistent elevation in mean and minimum 24-h body temperature of at least 0.5 °C. Corresponding behavioral data indicated that febrile monkeys spent more time resting and less time feeding, consistent with the known sickness behaviors of lethargy and anorexia, respectively. We found no evidence that fevers influenced the time individuals spent socializing with conspecifics, suggesting social transmission of infection within a group is likely. Notably, febrile monkeys were targeted with twice as much aggression from their conspecifics and were six times more likely to become injured compared to afebrile monkeys. Our results suggest that sickness behavior, together with its agonistic consequences, can carry meaningful costs for highly gregarious mammals. The degree to which social factors modulate the welfare of infected animals is an important aspect to consider when attempting to understand the ecological implications of disease.

A modified physiological strain index for workplace-based assessment of heat strain experienced by agricultural workers.

BACKGROUND: As global temperatures rise, increasing numbers of individuals will work in hot environments. Interventions to protect their health are critical, as are reliable methods to measure the physiological strain experienced from heat exposure. The physiological strain index (PSI) is a measure of heat strain that relies on heart rate and core temperature but is challenging to calculate in a real-world occupational setting. METHODS: We modified the PSI for use in field settings where resting temperature and heart rate are not available and used the modified physiological strain index (mPSI) to describe risk factors for high heat strain (mPSI ≥ 7) experienced by agricultural workers in Florida during the summers of 2015 through 2017. mPSI was calculated for 221 workers, yielding 465 days of data. RESULTS: A higher heat index (ß = 0.185; 95% CI: 0.064, 0.307) and higher levels of physical activity at work (0.033; 95% CI: 0.017, 0.050) were associated with a higher maximum mPSI. More years worked in US agriculture (-0.041; 95% CI: -0.061, -0.020) were protective against a higher maximum mPSI. Out of 23 workdays that a participant experienced a maximum mPSI ≥ 7, 22 were also classified as strained by at least one other measure of high heat strain (core temperature [Tc] >38.5°C, sustained heart rate >(180 - age), and mean heart rate > 115 bpm). CONCLUSIONS: This study provides critical information on risk factors for elevated heat strain for agricultural workers and suggests a practical approach for using PSI in field-based settings.

Thermography for the differential diagnosis of vascular malformations.

Vascular malformations classification may pose a diagnostic challenge for physicians. In the early stages, they are diagnosed clinically mainly by visual inspection. For a deeper analysis, Doppler ultrasonography is the preferred technique to determine the haemodynamic behaviour of the anomaly. However, this imaging method is not always available and it requires trained operators to acquire and interpret the images. There is a lack of portable and user-friendly systems that may help physicians in the assessment of vascular malformations. We propose a new diagnostic procedure, more affordable and easier to use, based on a portable thermal camera. This technique provides information about temperature, which has been found to be correlated with the flow rate of the lesion. In our study, > 60 vascular malformations of previously diagnosed patients were analysed with a thermal camera to classify them into low-flow and high-flow malformations. The value was 1 for both sensitivity and specificity of this technique.

Is Physiological Equivalent Temperature (PET) a superior screening tool for heat stress risk than Wet-Bulb Globe Temperature (WBGT) index? Eight years of data from the Gothenburg half marathon.

BACKGROUND: The Wet-Bulb Globe Temperature (WBGT) index is a common tool to screen for heat stress for sporting events. However, the index has a number of limitations. Rational indices, such as the physiological equivalent temperature (PET) and Universal Thermal Climate Index (UTCI), are potential alternatives. AIM: To identify the thermal index that best predicts ambulance-required assistances and collapses during a city half marathon. METHODS: Eight years (2010-2017) of meteorological and ambulance transport data, including medical records, from Gothenburg's half-marathon were used to analyse associations between WBGT, PET and UTCI and the rates of ambulance-required assistances and collapses. All associations were evaluated by Monte-Carlo simulations and leave-one-out-cross-validation. RESULTS: The PET index showed the strongest correlation with both the rate of ambulance-required assistances (R2=0.72, p=0.008) and collapses (R2=0.71, p=0.008), followed by the UTCI (R2=0.64, p=0.017; R2=0.64, p=0.017) whereas the WBGT index showed substantially poorer correlations (R2=0.56, p=0.031; R2=0.56, p=0.033). PET stages of stress, match the rates of collapses better that the WBGT flag colour warning. Compared with the PET, the WBGT underestimates heat stress, especially at high radiant heat load. The rate of collapses increases with increasing heat stress; large increase from the day before the race seems to have an impact of the rate of collapses. CONCLUSION: We contend that the PET is a better predictor of collapses during a half marathon than the WBGT. We call for further investigation of PET as a screening tool alongside WBGT.

A comprehensive assessment of multi-system responses to a renal inoculation of uropathogenic E. coli in swine.

BACKGROUND: The systemic responses to infection and its progression to sepsis remains poorly understood. Progress in the field has been stifled by the shortcomings of experimental models which include poor replication of the human condition. To address these challenges, we developed and piloted a novel large animal model of severe infection that is capable of generating multi-system clinically relevant data. METHODS: Male swine (n = 5) were anesthetized, mechanically ventilated, and surgically instrumented for continuous hemodynamic monitoring and serial blood sampling. Animals were inoculated with uropathogenic E. coli by direct injection into the renal parenchyma and were maintained until a priori endpoints were met. The natural history of the infection was studied. Animals were not resuscitated. Multi-system data were collected hourly to 6 hours; all animals were euthanized at predetermined physiologic endpoints. RESULTS: Core body temperature progressively increased from mean (SD) 37.9(0.8)°C at baseline to 43.0(1.2)°C at experiment termination (p = 0.006). Mean arterial pressure did not begin to decline until 6h post inoculation, dropping from 86(9) mmHg at baseline to 28(5) mmHg (p = 0.005) at termination. Blood glucose progressively declined but lactate levels did not elevate until the last hours of the experiment. There were also temporal changes in whole blood concentrations of a number of metabolites including increases in the catecholamine precursors, tyrosine (p = 0.005) and phenylalanine (p = 0.005). Lung, liver, and kidney function parameters worsened as infection progressed and at study termination there was histopathological evidence of injury in these end-organs. CONCLUSION: We demonstrate a versatile, multi-system, longitudinal, swine model of infection that could be used to further our understanding of the mechanisms that underlie infection-induced multi-organ dysfunction and failure, optimize resuscitation protocols and test therapeutic interventions. Such a model could improve translation of findings from the bench to the bedside, circumventing a significant obstacle in sepsis research.

Assessment of rewarming methods in unplanned out-of-hospital births from a prospective cohort.

BACKGROUND: Mobile intensive care units frequently manage unplanned out-of-hospital births (UOHB). Rewarming methods during pre-hospital management of UOHB have not yet been compared. The aim was to compare rewarming methods used during pre-hospital management in a large prospective cohort of UOHB in France. METHODS: We analysed UOHB from the prospective AIE cohort from 25 prehospital emergency medical services in France. The primary outcome was the change in body temperature from arrival at scene to arrival at hospital. RESULTS: From 2011 to 2018, 1854 UOHB were recorded, of whom 520 were analysed. We found that using incubator care was the most effective rewarming method (+ 0.8 °C during transport), followed by the combination of plastic bag, skin-to-skin and cap (+ 0.2 °C). The associations plastic bag + cap and skin-to-skin + cap did not allow the newborn to be warmed up but rather to maintain initial temperature (+ 0.0 °C). The results of the multivariate model were consistent with these observations, with better rewarming with the use of an incubator. We also identified circumstances of increased risk of hypothermia according to classification and regression tree, like premature birth (< 37 weeks of gestation) and/or low outside temperature (< 8.4 °C). CONCLUSIONS: Using an incubator was the most effective rewarming method during pre-hospital management of UOHB in our French prospective cohort. Based on our model, in cases of term less than 37 weeks of gestation or between 37 and 40 weeks with a low outside temperature or initial hypothermia, using such a method would be preferred.

An In Vivo Assessment of Regional Brain Temperature during Whole-Body Cooling for Neonatal Encephalopathy.

OBJECTIVE: To assess differences in regional brain temperatures during whole-body hypothermia and test the hypothesis that brain temperature profile is nonhomogenous in infants with hypoxic-ischemic encephalopathy. STUDY DESIGN: Infants with hypoxic-ischemic encephalopathy were enrolled prospectively in this observational study. Magnetic resonance (MR) spectra of basal ganglia, thalamus, cortical gray matter, and white matter (WM) were acquired during therapeutic hypothermia. Regional brain tissue temperatures were calculated from the chemical shift difference between water signal and metabolites in the MR spectra after performing calibration measurements. Overall difference in regional temperature was analyzed by mixed-effects model; temperature among different patterns and severity of injury on MR imaging also was analyzed. Correlation between temperature and depth of brain structure was analyzed using repeated-measures correlation. RESULTS: In total, 53 infants were enrolled (31 girls, mean gestational age: 38.6 ± 2 weeks; mean birth weight: 3243 ± 613 g). MR spectroscopy was acquired at mean age of 2.2 ± 0.6 days. A total of 201 MR spectra were included in the analysis. The thalamus, the deepest structure (36.4 ± 2.3 mm from skull surface), was lowest in temperature (33.2 ± 0.8°C, compared with basal ganglia: 33.5 ± 0.9°C; gray matter: 33.6 ± 0.7°C; WM: 33.8 ± 0.9°C, all P < .001). Temperatures in more superficial gray matter and WM regions (depth: 21.9 ± 2.4 and 21.5 ± 2.2 mm) were greater than the rectal temperatures (33.4 ± 0.4°C, P < .03). There was a negative correlation between temperature and depth of brain structure (rrm = -0.36, P < .001). CONCLUSIONS: Whole-body hypothermia was effective in cooling deep brain structures, whereas superficial structures were warmer, with temperatures significantly greater than rectal temperatures.

Body Temperature and Energy Expenditure During and After Yoga Breathing Practices Traditionally Described as Cooling.

BACKGROUND In traditional yoga texts, sheetali and sitkari pranayamas are described as cooling. The present study was aimed at recording the surface body temperature, oxygen consumed, and carbon dioxide eliminated before, during, and after performance of sheetali and sitkari pranayamas. MATERIAL AND METHODS Seventeen healthy male volunteers with ages between 19 to 25 years (average age 20.7±1.8 years) were assessed in 4 sessions, viz. sheetali pranayama, sitkari pranayama, breath awareness and quiet lying, on 4 separate days, in random sequence. The axillary surface body temperature (TRUSCOPE II, Schiller, China) and metabolic variables (Quark CPET, COSMED, Italy) were recorded in 3 periods: before (5 minutes), during (18 minutes), and after (5 minutes), in each of the 4 sessions. The heat index was calculated in the before and after periods, based on recordings of ambient temperature and humidity. Data were analyzed using SPSS (Version 24.0). RESULTS Body temperature increased significantly during sheetali and sitkari (p<0.05, p<0.01; respectively) while it decreased after breath awareness and quiet lying down (p<0.01, p<0.001; respectively) when compared with respective post-exercise states. Oxygen consumption increased by 9.0% during sheetali (p<0.05) and by 7.6% during sitkari (p<0.01) while it decreased significantly during (p<0.05) and after (p<0.01) quiet lying down compared to respective pre-exercise states. CONCLUSIONS The results do not support the description of these yoga breathing practices as cooling. These yoga breathing practices may be used to induce a mild hypermetabolic state.

Detection and Prediction of Ovulation From Body Temperature Measured by an In-Ear Wearable Thermometer.

OBJECTIVE: We present a non-invasive wearable device for fertility monitoring and propose an effective and flexible statistical learning algorithm to detect and predict ovulation using data captured by this device. METHODS: The system consists of an earpiece, which measures the ear canal temperature every 5 min during night sleep hours, and a base station that transmits data to a smartphone application for analysis. We establish a data-cleaning protocol for data preprocessing and then fit a Hidden Markov Model (HMM) with two hidden states of high and low temperature to identify the more probable state of each time point via the predicted probabilities. Finally, a post-processing procedure is developed to incorporate biorhythm information to form a time-course biphasic profile for each subject. RESULTS: The performance of the proposed algorithms applied to data collected by the device are compared with traditional methods in terms of match rate with self-reported ovulation days confirmed with an ovulation test kit. Empirical study results from a group of 34 users yielded significant improvements over the traditional methods in terms of detection accuracy (with sensitivity 92.31%) and prediction power (23.07-31.55% higher). CONCLUSION: We demonstrated the feasibility for reliable ovulation detection and prediction with high-frequency temperature data collected by a non-invasive wearable device. SIGNIFICANCE: Traditional fertility monitoring methods are often either inaccurate or inconvenient. The wearable device and learning algorithm presented in this paper provide a user friendly and reliable platform for tracking ovulation, which may have a broad impact on both fertility research and real-world family planning.

Priority based health data monitoring with IEEE 802.11af technology in wireless medical sensor networks.

In this work, the IEEE 802.11af technology-based wireless sensor network for health data monitoring with priority classes is proposed. In IEEE 802.11af technology, a White Space Device (WSD), a Station (STA), and an Access Point (AP) communicate through television white spectrum opportunistically without causing any harmful interference to licensed` services. In the proposed network; WSDs, STA, and AP employ Frequency Division Multiple Access (FDMA) technique with the aim of communicating through the white space spectrum determined by White Space Map (WSM). WSD collects health data such as body temperature and blood pressure from an implant or on-body sensors. The priority class is determined according to the emergency of a patient as red, yellow, and green. After obtaining the analytical model of the proposed network, the simulation model is carried out using Riverbed Modeler. The graphical results prove the validity and applicability of the proposed network in terms of delay (0.17 s) and energy consumption (4.7 mJ/s) without any spectrum cost for priority-based health data monitoring. Graphical abstract Cognitive radio based IEEE 802.11af environment for priority based health data monitoring.

[Changes in selected physiological indicators and thermal stress assessment under the influence of baths in a dry and wet sauna in young healthy women]. / Zmiany wybranych wskazników fizjologicznych oraz ocena stresu cieplnego pod wplywem kapieli w saunie suchej i mokrej u mlodych zdrowych kobiet.

BACKGROUND: There are differences between dry and wet sauna baths because of the heat load and human body's reactions. High humidity in a wet sauna makes evaporation of sweat from the skin surface more difficult. In addition, the dynamics of sweating is different in men and women. The aim of the study was to assess changes in physiological indicators and to compare the impact of dry and wet saunas on the thermal comfort feeling, which was assessed using the Bedford thermal scale, and the physiological strain index (PSI) and the cumulative heat stress index (CHSI) in young healthy women. MATERIAL AND METHODS: Ten women aged 22-24 years took part in the study. A session in each sauna lasted 60 min and consisted of 3 thermal 15-min exposures, in 5-min intervals for rest and cooling with water. The temperature in the dry sauna was 91±1.2°C and in the wet sauna 59±1.3°C, while the humidity was 18±0.7% and 60.5±0.8%, respectively. Body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), rectal temperature (Tre) and the thermal sensation (Bedford scale) were also measured. The PSI and CHSI values were both calculated. RESULTS: The average weight loss after a dry sauna bath was significantly higher than after a wet sauna bath. Significantly higher increases in Tre, as well as in HR were observed after treatment in the wet sauna, compared to the dry sauna. Both treatments resulted in an increase in SBP and a decrease in DBP. The arduousness of thermal discomfort and the levels of PSI and CHSI were skurgreater in the wet sauna bathing than in the dry sauna. CONCLUSIONS: Heat exposure in the wet sauna creates a greater burden for young women's bodies than the same dry sauna treatment, and the changes observed in the examined traits were higher than in men subjected to similar thermal loads. Med Pr. 2019;70(6):701-10.

Health assessment of Conolophus subcristatus, Conolophus pallidus, and C. subcristatus X Amblyrhynchus cristatus hybrid (Galápagos land iguanas).

The land iguanas, Conolophus pallidus and Conolophus subcristatu are large and charismatic lizards endemic to the Galápagos archipelago, but little information exists on their normal health parameters. The former is restricted to Santa Fe island, while C. subcristatus inhabits the islands of the central and western region of the archipelago. Both species are classified as vulnerable by the IUCN Red List of Threatened Species. As part of a population health assessment authorized by the Galápagos National Park, wild adult iguanas from three islands (North Seymour, South Plazas, and Santa Fe) were captured in July 2018. Data from a single C. subcristatus X Amblyrhynchus cristatus hybrid captured on South Plazas is also included. We analyzed blood samples drawn from 52 healthy wild adult land iguanas captured on three islands. An iSTAT portable blood analyzer was used to obtain values for pH, lactate, pO2, pCO2, HCO3-, sO2%, hematocrit, packed cell volume (PCV), hemoglobin Na, K, iCa, and glucose. Standard laboratory hematology techniques were employed for PCV determination; resulting values were also compared to the hematocrit values generated by the iSTAT. Body temperature, heart rate, respiratory rate, and body measurements were also recorded and compared to previously published data for the marine iguana (Amblyrhynchus cristatus), which shares a common ancestor with the land iguana. The data reported here provide preliminary baseline values that may be useful in comparisons between captive and wild populations, between wild populations, and in detecting changes in health status among Galápagos land iguanas affected by anthropogenic threats, climate change, or natural disturbances.

Predictability of individual circadian phase during daily routine for medical applications of circadian clocks.

BACKGROUNDCircadian timing of treatments can largely improve tolerability and efficacy in patients. Thus, drug metabolism and cell cycle are controlled by molecular clocks in each cell and coordinated by the core body temperature 24-hour rhythm, which is generated by the hypothalamic pacemaker. Individual circadian phase is currently estimated with questionnaire-based chronotype, center-of-rest time, dim light melatonin onset (DLMO), or timing of core body temperature (CBT) maximum (acrophase) or minimum (bathyphase).METHODSWe aimed at circadian phase determination and readout during daily routines in volunteers stratified by sex and age. We measured (a) chronotype, (b) every minute (q1min) CBT using 2 electronic pills swallowed 24 hours apart, (c) DLMO through hourly salivary samples from 1800 hours to bedtime, and (d) q1min accelerations and surface temperature at anterior chest level for 7 days, using a teletransmitting sensor. Circadian phases were computed using cosinor and hidden Markov modeling. Multivariate regression identified the combination of biomarkers that best predicted core temperature circadian bathyphase.RESULTSAmong the 33 participants, individual circadian phases were spread over 5 hours, 10 minutes (DLMO); 7 hours (CBT bathyphase); and 9 hours, 10 minutes (surface temperature acrophase). CBT bathyphase was accurately predicted, i.e., with an error less than 1 hour for 78.8% of the subjects, using a new digital health algorithm (INTime), combining time-invariant sex and chronotype score with computed center-of-rest time and surface temperature bathyphase (adjusted R2 = 0.637).CONCLUSIONINTime provided a continuous and reliable circadian phase estimate in real time. This model helps integrate circadian clocks into precision medicine and will enable treatment timing personalization following further validation.FUNDINGMedical Research Council, United Kingdom; AP-HP Foundation; and INSERM.

Nesting box imager: Contact-free, real-time measurement of activity, surface body temperature, and respiratory rate applied to hibernating mouse models.

Noncontact methods to measure animal activity and physiology are necessary to monitor undisturbed states such as hibernation. Although some noncontact measurement systems are commercially available, they are often incompatible with realistic habitats, which feature freely moving animals in small, cluttered environments. A growing market of single-board computers, microcontrollers, and inexpensive sensors has made it possible to assemble bespoke integrated sensor systems at significantly lower price points. Herein, we describe a custom-built nesting box imager (NBI) that uses a single-board computer (Raspberry Pi) with a passive infrared (IR) motion sensor, silicon charge-coupled device (CCD), and IR camera CCD to monitor the activity, surface body temperature, and respiratory rate of the meadow jumping mouse during hibernation cycles. The data are logged up to 12 samples per minute and postprocessed using custom Matlab scripts. The entire unit can be built at a price point below US$400, which will be drastically reduced as IR (thermal) arrays are integrated into more consumer electronics and become less expensive.

Telemetered common marmosets is useful for the assessment of electrocardiogram parameters changes induced by multiple cardiac ion channel inhibitors.

The objective of this study is to assess the response of telemetered common marmosets to multiple cardiac ion channel inhibitors and to clarify the usefulness of this animal model in evaluating the effects of drug candidates on electrocardiogram (ECG). Six multiple cardiac ion channel inhibitors (sotalol, astemizole, flecainide, quinidine, verapamil and terfenadine) were orally administered to telemetered common marmosets and changes in QTc, PR interval and QRS duration were evaluated. Drugs plasma levels were determined to compare the sensitivity in common marmosets to that in humans. QTc prolongation was observed in the marmosets dosed with sotalol, astemizole, flecainide, quinidine, verapamil and terfenadine. PR prolongation was noted after flecainide and verapamil administration, and QRS widening occurred following treatment with flecainide and quinidine. Drugs plasma levels associated with ECG changes in marmosets were similar to those in humans, except for verapamil-induced QTc prolongation. Verapamil-induced change is suggested due to body temperature decrease. These results indicate that telemetered common marmoset is a useful animal for evaluation of the ECG effects of multiple cardiac ion channel inhibitors and the influence of body temperature change should be considered in the assessment.

Heat stress assessment during intermittent work under different environmental conditions and clothing combinations of effective wet bulb globe temperature (WBGT).

This study examined whether different combinations of ambient temperature and relative humidity for the effective wet bulb globe temperature, in conjunction with two different levels of clothing adjustment factors, elicit a similar level of heat strain consistent with the current threshold limit value guidelines. Twelve healthy, physically active men performed four 15-min sessions of cycling at a fixed rate of metabolic heat production of 350 watts. Each trial was separated by a 15-min recovery period under four conditions: (1) Cotton coveralls + dry condition (WD: 45.5 °C dry-bulb, 15% relative humidity); (2) Cotton coveralls + humid condition (WH: 31 °C dry-bulb, 84% relative humidity); (3) Protective clothing + dry condition (PD: 30 °C dry-bulb, 15% relative humidity); and (4) Protective clothing + humid condition (PH: 20 °C dry-bulb, 80% relative humidity). Gloves (mining or chemical) and headgear (helmet or powered air-purifying respirator) were removed during recovery with hydration ad libitum. Rectal temperature (Tre), skin temperature (Tsk), physiological heat strain (PSI), perceptual heat strain (PeSI), and body heat content were calculated. At the end of the 2-hr trials, Tre remained below 38 °C and the magnitude of Tre elevation was not greater than 1 °C in all conditions (WD: 0.9, WH: 0.8, WH: 0.7, and PD: 0.6 °C). However, Tsk was significantly increased by approximately 2.1 ± 0.8 °C across all conditions (all p ≤ 0.001). The increase in Tsk was the highest in WD followed by PD, WH, and PH conditions (all p ≤ 0.001). Although PSI and PeSI did not indicate severe heat strain during the 2-hr intermittent work period, PSI and PeSI were significantly increased over time (p ≤ 0.001). This study showed that core temperature and heat strain indices (PSI and PeSI) increased similarly across the four conditions. However, given that core temperature increased continuously during the work session, it is likely that the American Conference of Governmental Industrial Hygienist's TLV® upper limit core temperature of 38.0 °C may be surpassed during extended work periods under all conditions.