Factors contributing to heat tolerance in humans & experimental models.

Understanding physiological mechanisms of tolerance to heat exposure, and potential ways to improve such tolerance, is increasingly important in the context of ongoing climate change. We discuss the concept of heat tolerance in humans and experimental models (primarily rodents), including intracellular mechanisms and improvements in tolerance with heat acclimation.

Female thermal sensitivity and behaviour across the lifespan: A unique journey.

Women are a group of individuals that undergo unique anatomical, physiological and hormonal changes across the lifespan. For example, consider the impact of the menstrual cycle, pregnancy and menopause, all of which are accompanied by both short- and long-term effects on female body morphology (e.g., changes in breast size) and temperature regulation, heat tolerance, thermal sensitivity and comfort. However, empirical evidence on how skin thermal and wetness sensitivity might change across the lifespan of women, and the implications that this has for female-specific thermal behaviours, continues to be lacking. This paper is based on a symposium presentation given at Physiology 2023 in Harrogate, UK. It aims to review new evidence on anatomical and physiological mechanisms underpinning differences in skin thermal and wetness sensitivity amongst women varying in breast size and age, in addition to their role in driving female thermal behaviours. It is hoped that this brief overview will stimulate the development of testable hypotheses to increase our understanding of the behavioural thermal physiology of women across the lifespan and at a time of climate change.

Heat-related risk at Paris 2024: a proposal for classification and review of International Federations policies.

Several International Federations (IFs) employ specific policies to protect athletes' health from the danger of heat. Most policies rely on the measurement of thermal indices such as the Wet Bulb Globe Temperature (WBGT) to estimate the risk of heat-related illness. This review summarises the policies implemented by the 32 IFs of the 45 sports included in the Paris 2024 Olympic Games. It provides details into the venue type, measured parameters, used thermal indices, measurement procedures, mitigation strategies and specifies whether the policy is a recommendation or a requirement. Additionally, a categorisation of sports' heat stress risk is proposed. Among the 15 sports identified as high, very high or extreme risk, one did not have a heat policy, three did not specify any parameter measurement, one relied on water temperature, two on air temperature and relative humidity, seven on WBGT (six measured on-site and one estimated) and one on the Heat Stress Index. However, indices currently used in sports have been developed for soldiers or workers and may not adequately reflect the thermal strain endured by athletes. Notably, they do not account for the athletes' high metabolic heat production and their level of acclimation. It is, therefore, worthwhile listing the relevance of the thermal indices used by IFs to quantify the risk of heat stress, and in the near future, develop an index adapted to the specific needs of athletes.

High-density thermal sensitivity maps of the body of people with multiple sclerosis: Implications for inclusive personal comfort systems.

Inclusive thermal comfort solutions should accommodate the need of clinical groups such as people with Multiple Sclerosis (pwMS), who experience abnormal thermal sensitivity. The aim of this study was to develop high-density body maps of temperature sensitivity in pwMS to inform the design of patient-centred personal comfort systems. Fourteen pwMS (6 M/8 F; 48.6 ± 10.0 y) and 13 healthy individuals (CTR; 5 M/8 F; 47.8 ± 10.4) underwent a quantitative sensory test in a thermoneutral environment, during which they rated their local thermal sensations arising from the application of warm (39°C) and cold (27°C) stimuli to 115 bilateral body sites across the face, torso, upper and lower limbs. We used a z-transformation to create maps of hypo- and hyper-sensitivity for each individual MS participant using normative CTR data. We found that 50% of pwMS (N = 7/14) presented a loss of cold sensitivity over the upper limb, and a loss of warm sensitivity over the feet. Furthermore, 36% of pwMS (N = 5) presented warm hyper-sensitivity over the upper limb. Finally, cold sensitivity loss and warm sensitivity gain were more evenly distributed and affected a greater proportion of skin sites in MS (i.e. cold hypo-sensitivity = 44% of tested sites; warm hyper-sensitivity = 14%) than warm sensitivity loss (i.e. 10%), which was more focused on sites such as the feet. Our findings highlight the need to consider "thermosensory corrective power" when designing personal comfort systems, to accommodate either thermosensory loss or gain in pwMS. Our approach to clinical body mapping may support this process and help meeting the unique thermal needs of vulnerable individuals.

The Effect of Brief Warming during Induction of General Anesthesia and Warmed Intravenous Fluid on Intraoperative Hypothermia in Patients Undergoing Urologic Surgery.

Background and Objectives: Transurethral urologic surgeries frequently lead to hypothermia due to bladder irrigation. Prewarming in the preoperative holding area can reduce the risk of hypothermia but disrupts surgical workflow, preventing it from being of practical use. This study explored whether early intraoperative warming during induction of anesthesia, known as peri-induction warming, using a forced-air warming device combined with warmed intravenous fluid could prevent intraoperative hypothermia. Materials and Methods: Fifty patients scheduled for transurethral resection of the bladder (TURB) or prostate (TURP) were enrolled and were randomly allocated to either the peri-induction warming or control group. The peri-induction warming group underwent whole-body warming during anesthesia induction using a forced-air warming device and was administered warmed intravenous fluid during surgery. In contrast, the control group was covered with a cotton blanket during anesthesia induction and received room-temperature intravenous fluid during surgery. Core temperature was measured upon entrance to the operating room (T0), immediately after induction of anesthesia (T1), and in 10 min intervals until the end of the operation (Tend). The incidence of intraoperative hypothermia, change in core temperature (T0-Tend), core temperature drop rate (T0-Tend/[duration of anesthesia]), postoperative shivering, and postoperative thermal comfort were assessed. Results: The incidence of intraoperative hypothermia did not differ significantly between the two groups. However, the peri-induction warming group exhibited significantly less change in core temperature (0.61 ± 0.3 °C vs. 0.93 ± 0.4 °C, p = 0.002) and a slower core temperature drop rate (0.009 ± 0.005 °C/min vs. 0.013 ± 0.004 °C/min, p = 0.013) than the control group. The peri-induction warming group also reported higher thermal comfort scores (p = 0.041) and less need for postoperative warming (p = 0.034) compared to the control group. Conclusions: Brief peri-induction warming combined with warmed intravenous fluid was insufficient to prevent intraoperative hypothermia in patients undergoing urologic surgery. However, it improved patient thermal comfort and mitigated the absolute amount and rate of temperature drop.

Induction and decay of seasonal acclimatization on whole body heat loss responses during exercise in a hot humid environment with different air velocities.

Whether whole body heat loss and thermoregulatory function (local sweat rate and skin blood flow) are different between summer and autumn and between autumn and winter seasons during exercise with different air flow in humid heat remain unknown. We therefore tested the hypotheses that whole body sweat rate (WBSR), evaporated sweat rate, and thermoregulatory function during cycling exercise in autumn would be higher than in winter but would be lower than in summer under hot-humid environment (32 C, 75% RH). We also tested the hypothesis that the increase of air velocity would enhance evaporated sweat rate and sweating efficiency across winter, summer, and autumn seasons. Eight males cycled for 1 h at 40% V̇o2max in winter, summer, and autumn seasons. Using an electric fan, air velocity increased from 0.2 m/s to 1.1 m/s during the final 20 min of cycling. The autumn season resulted in a lower WBSR, unevaporated sweat rate, and a higher sweating efficiency compared with summer (all P ≤ 0.05) but WBSR and unevaporated sweat rate in autumn were higher than in winter and thus sweating efficiency was lower when compared with winter only at the air velocity of 0.2 m/s (All P ≤ 0.05). Furthermore, evaporated sweat rate and core temperature (Tcore) were not different among winter, summer, and autumn seasons (All P > 0.19). In conclusion, changes in WBSR across different seasons do not alter Tcore during exercise in a hot humid environment. Furthermore, increasing air velocity enhances evaporated sweat rate and sweating efficiency across all seasons.

Myotendinous Thermoregulation in National Level Sprinters after a Unilateral Fatigue Acute Bout-A Descriptive Study.

In the last decade there has been a growing interest in infrared thermography in the field of sports medicine in order to elucidate the mechanisms of thermoregulation. The aim of this study was to describe bilateral variations in skin temperature of the anterior thigh and patellar tendon in healthy athletes and to provide a model of baseline tendon and muscle thermoregulation in healthy sprinters following a unilateral isokinetic fatigue protocol. Fifteen healthy national-level sprinters (eleven men and four women), with at least 3 years of athletic training experience of 10-12 h/week and competing in national-level competitions, underwent unilateral isokinetic force testing and electrostimulation in which their body temperature was measured before, during, and after the protocol using an infrared thermographic camera. ANOVA detected a significant difference in the time × side interaction for patellar temperature changes (p ≤ 0.001) and a significant difference in the time/side interaction for quadriceps temperature changes (p ≤ 0.001). The thermal challenge produces homogeneous changes evident in quadriceps areas, but not homogeneous in tendon areas. These data show that metabolic and blood flow changes may depend on the physical and mechanical properties of each tissue. Future research could be conducted to evaluate the predictive value of neuromuscular fatigue in the patellar tendon and quadriceps after exercise in order to optimize post-exercise recovery strategies.

Implications of the Onset of Sweating on the Sweat Lactate Threshold.

The relationship between the onset of sweating (OS) and sweat lactate threshold (sLT) assessed using a novel sweat lactate sensor remains unclear. We aimed to investigate the implications of the OS on the sLT. Forty healthy men performed an incremental cycling test. We monitored the sweat lactate, blood lactate, and local sweating rates to determine the sLT, blood LT (bLT), and OS. We defined participants with the OS during the warm-up just before the incremental test as the early perspiration (EP) group and the others as the regular perspiration (RP) group. Pearson's correlation coefficient analysis revealed that the OS was poorly correlated with the sLT, particularly in the EP group (EP group, r = 0.12; RP group, r = 0.56). Conversely, even in the EP group, the sLT was strongly correlated with the bLT (r = 0.74); this was also the case in the RP group (r = 0.61). Bland-Altman plots showed no bias between the mean sLT and bLT (mean difference: 19.3 s). Finally, in five cases with a later OS than bLT, the sLT tended to deviate from the bLT (mean difference, 106.8 s). The sLT is a noninvasive and continuous alternative to the bLT, independent of an early OS, although a late OS may negatively affect the sLT.

Three dimensional models of human thermoregulation: A review.

Numerous human thermoregulatory models have been developed and widely used in various applications such as aerospace, medicine, public health, and physiology research. This paper is a review of three dimensional (3D) models for human thermoregulation. This review begins with a short introduction of thermoregulatory model development followed by key principles for mathematical description of human thermoregulation systems. Different representations of 3D human bodies are discussed with respect to their detail and prediction capability. The human body was divided into fifteen layered cylinders in early 3D models (cylinder model). Recent 3D models have utilized medical image datasets to develop geometrically correct human models (realistic geometry model). The finite element method is mostly used to solve the governing equations and get numerical solutions. The realistic geometry models provide a high degree of anatomical realism and predict whole-body thermoregulatory responses at high resolution and at organ and tissue levels. Thus, 3D models extend to a wide range of applications where temperature distribution is critical, such as hypothermia/hyperthermia therapy and physiology research. The development of thermoregulatory models will continue with the growth in computational power, advancement in numerical methods and simulation software, advances in modern imaging techniques, and progress in the basic science of thermal physiology.

Head cooling wrap could suppress the elevation of core temperature after cardiac surgery during forced-air warming in a pediatric intensive care unit: a randomized clinical trial.

PURPOSE: The main aim of the current trial was to explore our hypothesis that cooling head wraps lower the core temperature more effectively than ice packs on the head during forced-air warming after pediatric cardiac surgeries. METHODS: This study was a single-center Randomized Controlled Trial. Participants were children with a weight ≤ 10 kg and hyperthermia during forced-air warming after cardiac surgeries. When the core temperature reached 37.5 °C, ice packs on the head (group C) or a cooling head wrap (group H) were used as cooling devices to decrease the core temperature. The primary outcome was the core temperature. The secondary outcomes were the foot surface temperature and heart rate. We measured all outcomes every 30 min for 240 min after the patient developed hyperthermia. We conducted two-way ANOVA as a pre-planned analysis and also the Bonferroni test as a post hoc analysis. RESULTS: Twenty patients were randomly assigned to groups C and H. The series of core temperatures in group H were significantly lower than those in group C (p < 0.0001), and post hoc analysis showed that there was no significant difference in core temperatures at T0 between the two groups and statistically significant differences in all core temperatures at T30-240 between the two groups. There was no difference between the two groups' surface temperatures and heart rates. CONCLUSIONS: Compared to ice packs on the head, head cooling wraps more effectively suppress core temperature elevation during forced-air warming after pediatric cardiac surgery.

Regional skin wetness perception and its modulation by warm and cold whole body skin temperatures in people with multiple sclerosis.

Skin wetness sensing is important for thermal stress resilience. Individuals with multiple sclerosis (MS) present greater vulnerability to thermal stress; yet, it is unclear whether they present wetness-sensing abnormalities. We investigated the effects of MS on wetness sensing and their modulation with changes in mean skin temperature (Tsk). Twelve participants with MS [5 males (M)/7 females (F); 48.3 ± 10.8 yr; Expanded Disability Status Scale (EDSS) range: 1-7] and 11 healthy controls (4 M/7 F; 47.5 ± 11.3 yr) undertook three trials, during which they performed a quantitative sensory test with either a thermoneutral (30.9°C), warm (34.8°C), or cold (26.5°C) mean Tsk. Participants reported on visual analog scales local wetness perceptions arising from the static and dynamic application of a cold-, neutral-, and warm-wet probe (1.32 cm2; water content: 0.8 mL), to the index finger pad, forearm, and forehead. Data were analyzed for the group-level effect of MS, as well as for its individual variability. Our results indicated that MS did not alter skin wetness sensitivity at a group level, across the skin sites and temperature tested, neither under normothermia nor under conditions of shifted thermal state. However, when taking an individualized approach to profiling wetness-sensing abnormalities in MS, we found that 3 of the 12 participants with MS (i.e., 25% of the sample) presented a reduced wetness sensitivity on multiple skin sites and to different wet stimuli (i.e., cold, neutral, and warm wet). We conclude that some individuals with MS may possess reduced wetness sensitivity; however, this sensory symptom may vary greatly at an individual level. Larger-scale studies are warranted to characterize the mechanisms underlying such individual variability.

Duration of skin-to-skin care and rectal temperatures in late preterm and term infants.

BACKGROUND: Hypothermia during the newborn period is widely regarded as a major contributory cause of significant morbidity and mortality of newborn infants. Thermoprotective behaviours such as skin-to-skin care (SSC) or the use of appropriate devices have been recommended as simple tools for the avoidance of neonatal hypothermia. We examined the relation between the duration of skin-to-skin care and infant temperature change after birth in suboptimal delivery room temperatures. METHODS: We reviewed the medical charts of all vaginally born infants of gestational age ≥ 35 weeks born January-July 2018 and admitted to the well-baby nursery. After SSC was discontinued, the infant's rectal temperature was measured to determine the frequency and severity of hypothermia. RESULTS: The charts of 688 vaginally born infants were examined. Our mean delivery room temperature was 21.7 (SD 2.2) °C, well below the WHO recommendation of 25 °C. After SSC 347 (50.4%) infants were normothermic (temperature 36.5-37.5 °C), 262 (38.0%) were mildly hypothermic (36.0-36.4 °C), and 79 (11.4%) were moderately hypothermic (32.0-35.9 °C). The mean skin-to-skin time in infants was 63.9 (SD 20.9) minutes. SSC duration was associated with increase in rectal temperature for patients of gestational ages ≥ 38 weeks and with decrease in rectal temperature in patients of gestational age < 38 weeks. CONCLUSION: SSC is effective, even at suboptimal delivery room temperatures, for promoting normothermia in infants of ≥ 38 weeks' gestation but may not provide adequate warmth for infants of < 38 weeks.

Prehospital management of exertional heat stroke at sports competitions for Paralympic athletes.

OBJECTIVES: To adapt key components of exertional heat stroke (EHS) prehospital management proposed by the Intenational Olympic Committee Adverse Weather Impact Expert Working Group for the Olympic Games Tokyo 2020 so that it is applicable for the Paralympic athletes. METHODS: An expert working group representing members with research, clinical and lived sports experience from a Para sports perspective reviewed and revised the IOC consensus document of current best practice regarding the prehospital management of EHS. RESULTS: Similar to Olympic competitions, Paralympic competitions are also scheduled under high environmental heat stress; thus, policies and procedures for EHS prehospital management should also be established and followed. For Olympic athletes, the basic principles of EHS prehospital care are: early recognition, early diagnosis, rapid, on-site cooling and advanced clinical care. Although these principles also apply for Paralympic athletes, slight differences related to athlete physiology (eg, autonomic dysfunction) and mechanisms for hands-on management (eg, transferring the collapsed athlete or techniques for whole-body cooling) may require adaptation for care of the Paralympic athlete. CONCLUSIONS: Prehospital management of EHS in the Paralympic setting employs the same procedures as for Olympic athletes with some important alterations.

Realtime Monitoring of Local Sweat Rate Kinetics during Constant-Load Exercise Using Perspiration-Meter with Airflow Compensation System.

Epidermal wearable sweat biomarker sensing technologies are likely affected by sweat rate because of the dilution effect and limited measurement methods. However, there is a dearth of reports on the local sweat rate (LSR) monitored in real-time during exercise. This explorative study investigated the feasibility of real-time LSR monitoring and clarified LSR kinetics on the forehead and upper arm during constant-load exercise using a perspiration meter with an airflow compensation system. This observational cross-sectional study included 18 recreationally trained males (mean age, 20.6 ± 0.8 years). LSR on the forehead and upper arm (mg/cm2/min) were measured during a constant-load exercise test at 25% of their pre-evaluated peak power until exhaustion. The LSR kinetics had two inflection points, with a gradual decrease in the incremental slope for each section. After the second flexion point, the LSR slope slightly decreased and was maintained until exhaustion. However, the degree of change varied among the participants. Although the ratio of forehead LSR to upper arm LSR tended to decrease gradually over time, there was little change in this ratio after a second flexion point of LSR in both. These findings suggest possible differences in LSR control between the forehead and upper arm during constant-load exercise to prolonged exhaustion.

A specialized pore turret in the mammalian cation channel TRPV1 is responsible for distinct and species-specific heat activation thresholds.

The transient receptor potential vanilloid 1 (TRPV1) channel is a heat-activated cation channel that plays a crucial role in ambient temperature detection and thermal homeostasis. Although several structural features of TRPV1 have been shown to be involved in heat-induced activation of the gating process, the physiological significance of only a few of these key elements has been evaluated in an evolutionary context. Here, using transient expression in HEK293 cells, electrophysiological recordings, and molecular modeling, we show that the pore turret contains both structural and functional determinants that set the heat activation thresholds of distinct TRPV1 orthologs in mammals whose body temperatures fluctuate widely. We found that TRPV1 from the bat Carollia brevicauda exhibits a lower threshold temperature of channel activation than does its human ortholog and three bat-specific amino acid substitutions located in the pore turret are sufficient to determine this threshold temperature. Furthermore, the structure of the TRPV1 pore turret appears to be of physiological and evolutionary significance for differentiating the heat-activated threshold among species-specific TRPV1 orthologs. These findings support a role for the TRPV1 pore turret in tuning the heat-activated threshold, and they suggest that its evolution was driven by adaption to specific physiological traits among mammals exposed to variable temperatures.

Ageing reduces skin wetness sensitivity across the body.

NEW FINDINGS: What is the central question of this study? Ageing impairs the skin's thermal and tactile sensitivity: does ageing also induce loss of skin wetness sensitivity? What is the main finding and its importance? Older adults show an average 15% loss of skin wetness sensitivity, with this sensory deficit being mediated by a combination of reductions in skin's tactile sensing and hydration status. These findings increase knowledge of wetness sensing mechanisms across the lifespan. ABSTRACT: Humans use sensory integration mechanisms to sense skin wetness based on thermal and mechanical cues. Ageing impairs the skin's thermal and tactile sensitivity, yet we lack evidence on whether wetness sensing also changes with ageing. We mapped local skin wetness and temperature sensitivity in response to cold-, neutral- and warm-wet stimuli applied to the forehead, neck, lower back, dorsal foot, index finger and thumb, in 10 Younger (22.4 ± 1.1 years) and 10 Older (58.2 ± 5.1 years) males. We measured local skin temperature and conductance (i.e., a marker of hydration status) at the tested sites, to establish the role of skin's thermal and mechanical parameters in ageing-induced changes in wetness sensing. Irrespective of body site, Older reported overall lower wetness perceptions than Younger across all wet-stimulus temperatures (mean difference: -14.6 mm; 95% CI: -4.3, -24.9; P = 0.008; ∼15% difference). When considering regional wetness sensitivity, the effect of ageing was more pronounced in response to the cold-wet stimulus over the lover back (mean difference Older vs. Younger: -36.8 mm; 95% CI: -68.4, -5.2; P = 0.014; ∼37% difference) and dorsal foot (mean difference: -37.1 mm; 95% CI: -68.7, -5.5; P = 0.013; ∼37% difference). We found no differences between age groups on overall thermal sensations (P = 0.744) nor local skin temperature (P = 0.372); however, we found that Older presented overall lower skin conductance than Younger (mean difference: -1.56 µS; 95% CI: -0.49, -2.62; P = 0.005), which corresponded to an ∼78% reduction in skin hydration. We conclude that skin wetness sensing decreases with ageing primarily due to age-induced changes in skin mechanics and tactile sensitivity.

Oxytocin and 'social hyperthermia': Interaction with ß3-adrenergic receptor-mediated thermogenesis and significance for the expression of social behavior in male and female mice.

Oxytocin (OT) is a critical regulator of multiple facets of energy homeostasis, including brown adipose tissue (BAT) thermogenesis. Nevertheless, it is unclear what, if any, consequence the thermoregulatory and metabolic effects of OT have for the display of social behavior in adult rodents. Here, we examine the contribution of the OT receptor (OTR) and ß3 adrenergic receptor (ß3AR) to the increase in body temperature that typically accompanies social interaction (i.e., social hyperthermia; SH) and whether SH relates to the expression of social behavior in adult mice. Specifically, we examined how OTR antagonism via peripheral injection of L-368,899 (10 mg/kg) affects the expression of social behavior in C57BL/6J mice, in the presence of active/agonized versus antagonized ß3AR, the receptor known to mediate stress-induced BAT thermogenesis. After drug treatment and a 30 min delay, mice were provided a 10 min social interaction test with an unfamiliar, same-sex conspecific. We hypothesized that OTR and ß3AR/BAT interact to influence behavior during social interaction, with at least some effects of OT on social behavior dependent upon OT's thermal effects via ß3AR/BAT. We found that OTR-mediated temperature elevation is largely responsible for SH during social interaction in mice-albeit not substantially via ß3AR-dependent BAT thermogenesis. Further, our results reveal a complex relationship between OTR, ß3AR, social hyperthermia and the display of specific social behaviors, with SH most closely associated with anxiety and/or vigilance-related behaviors-that is, behaviors that antagonize or interfere with the initiation of close, non-agonistic social behavior.

Pyruvate induces torpor in obese mice.

Mice subjected to cold or caloric deprivation can reduce body temperature and metabolic rate and enter a state of torpor. Here we show that administration of pyruvate, an energy-rich metabolic intermediate, can induce torpor in mice with diet-induced or genetic obesity. This is associated with marked hypothermia, decreased activity, and decreased metabolic rate. The drop in body temperature correlates with the degree of obesity and is blunted by housing mice at thermoneutrality. Induction of torpor by pyruvate in obese mice relies on adenosine signaling and is accompanied by changes in brain levels of hexose bisphosphate and GABA as detected by mass spectroscopy-based imaging. Pyruvate does not induce torpor in lean mice but results in the activation of brown adipose tissue (BAT) with an increase in the level of uncoupling protein-1 (UCP1). Denervation of BAT in lean mice blocks this increase in UCP1 and allows the pyruvate-induced torpor phenotype. Thus, pyruvate administration induces torpor in obese mice by pathways involving adenosine and GABA signaling and a failure of normal activation of BAT.

Ecological constraints to match field and preferred temperatures in lizards Tropidurus catalanensis (Squamata; Tropiduridae).

We compared microhabitat and body temperatures in the field with thermal preferences of Tropidurus catalanensis to investigate if they match or diverge as demonstration respectively of suitability or poor-quality of the thermal environment. As T. catalanensis is subjected to variable thermal conditions along its distribution and may be jeopardized by the climate change, we measured its thermal preferences after exposure to milder (17 °C-27 °C) and warmer (22 °C-32 °C) thermal conditions to evaluate acclimatory responses and tolerances and vulnerabilities to warming. Field body temperatures tended to be similar to minimum preferred body temperatures, and microhabitat and body temperatures in the field were cooler in the remaining comparisons with thermal preferences [preferred (Tpref), set-point range (Tset), minimum preferred (Tpref_min) and maximum preferred (Tpref_max) body temperatures], suggesting there was a constraint to warming up in nature. The minimum preferred body temperatures may be a threshold separating proper functioning from markedly noxious impacts due to progressive impairment by the cooling. Difficulties to warm and keep suitable body temperatures may jeopardize overall ecophysiological and behavioral processes with implications for maintenance, fitness, and survival. The constraints to warm may impact T. catalanensis differently depending on its body size and its properties of heat conservation (thermal inertia). Smaller and larger T. catalanensis may respectively cool down easier and have difficulties to warm up, being jeopardized by the constraints due to the cold. The warmer preferred body temperatures coupled with the cooler microhabitats and bodies in nature complicate to anticipate how individuals will respond to climate change, but the acclimation to the warmer temperatures led six of them to death, suggesting they had limited tolerance to heat and would be vulnerable to global warming.

Active cooling temperature required to achieve therapeutic hypothermia correlates with short-term outcome in neonatal hypoxic-ischaemic encephalopathy.

KEY POINTS: Hypoxic-ischaemic encephalopathy (HIE) affects 2-4/1000 live term births. Treatment with therapeutic hypothermia (TH) improves the long-term neurodevelopmental outcome of neonates with moderate to severe HIE. However, early prediction of outcome still remains challenging, and no reliable and easily obtainable biomarker has been identified to date. Neonates with HIE display impaired thermoregulation, resulting in spontaneous hypothermia. The degree of cooling required to achieve TH may therefore act as a biomarker of injury severity. The present study demonstrates a correlation between servo-controlled mattress temperature during TH and short-term outcome. Neonates with an unfavourable outcome require less cooling to maintain a core temperature between 33 and 34°C during TH compared to neonates with a favourable outcome. The degree of impaired temperature regulation was strongly associated with a high magnetic resonance imaging injury score and death. Cooling device output temperature is a potential and easily obtainable early physiological biomarker of outcome in infants with HIE undergoing TH. ABSTRACT: Neonatal hypoxic-ischaemic encephalopathy (HIE) is a leading cause of death and disability in children. Therapeutic hypothermia (TH) at 33.5°C for 72 h is the only therapy to date shown to improve outcome in moderate to severe HIE; however, assessment of severity and prediction of outcome remains challenging. Infants with HIE display significant physiological perturbations, including spontaneous hypothermia. We hypothesized that neonates with more severe brain injury on magnetic resonance imaging (MRI) would exhibit a greater degree of spontaneous hypothermia, and thus require less active cooling to attain TH. Twenty-eight neonates with moderate or severe HIE treated with TH were included in the present study. MRI images obtained on day of life 4-7 were scored according to standardized injury criteria. Unfavourable outcome was defined as death or significant grey matter injury on MRI according to a previously validated scoring system. A significantly higher cooling device output temperature was seen in infants with an unfavourable outcome. All neonates who required the mattress to provide a temperature ≥32°C to maintain their core body temperature at 33.5°C had a high likelihood of unfavourable outcome (likelihood ratio = 14.4). By contrast, infants who never required a device output temperature ≥32°C had a low likelihood of an unfavourable outcome (likelihood ratio = 0.07, P < 0.001). Infants with significant grey matter injury on MRI require less active cooling to maintain target temperature during TH. The cooling device output temperature has the potential to be an easily accessible physiological biomarker and predictor of injury and mortality in neonates with moderate or severe HIE.