Elevated Core Body Temperature Research Articles

Heatguard: An ultra-low-cost three-dimensional-printed sensor for skin temperature alert and reporting system.

A heatstroke is one of the most serious forms of heat injury and is classified as a medical emergency. It is characterized by an elevated core body temperature along with the failed body cooling mechanism in response to the sudden heat-up. People vulnerable to a heatstroke are children, elders and sports professionals. Previous efforts have emphasized exercise adjustments and post-treatments, such as environmental-based activity modification and cold-water immersion. However, the general public, especially elders, will have difficulty to conduct such adjustments by themselves. Moreover, few studies have been conducted on the early preventive measurement stage. A wearable three-dimensional-printed thermochromic device proposed here can warn the people of a sudden rise in skin temperature and can advise them to take quick action. Combined with the smartphone applications, for both the android and iPhone platform, the device is able to monitor real-time skin temperature and alerts the people who are vulnerable to a heatstroke. The three-dimensional printable resin developed can change color at a specific activation temperature. The device has undergone a series of performance tests in order to optimize the color transition rate and stability of color change. The accuracy of our device is compared to the conventional thermometer; the regression analysis shows the R2 value is 0.7599 and the average error is 1.3 °C. Future work will be to mitigate the surrounding lighting effects on the smartphone camera and further improve our device accuracy.

Swimming strategies and energetics of endothermic white sharks during foraging.

Some fishes and sea turtles are distinct from ectotherms by having elevated core body temperatures and metabolic rates. Quantifying the energetics and activity of the regionally endothermic species will help us understand how a fundamental biophysical process (i.e. temperature-dependent metabolism) shapes animal ecology; however, such information is limited owing to difficulties in studying these large, highly active animals. White sharks, Carcharodon carcharias, are the largest fish with regional endothermy, and potentially among the most energy-demanding fishes. Here, we deployed multi-sensor loggers on eight white sharks aggregating near colonies of long-nosed fur seals, Arctocephalus forsteri, off the Neptune Islands, Australia. Simultaneous measurements of depth, swim speed (a proxy for swimming metabolic rate) and body acceleration (indicating when sharks exhibited energy-efficient gliding behaviour) revealed their fine-scale swimming behaviour and allowed us to estimate their energy expenditure. Sharks repeatedly dived (mean swimming depth, 29 m) and swam at the surface between deep dives (maximum depth, 108 m). Modal swim speeds (0.80-1.35 m s-1) were slower than the estimated speeds that minimize cost of transport (1.3-1.9 m s-1), a pattern analogous to a 'sit-and-wait' strategy for a perpetually swimming species. All but one shark employed unpowered gliding during descents, rendering deep (>50 m) dives 29% less costly than surface swimming, which may incur additional wave drag. We suggest that these behavioural strategies may help sharks to maximize net energy gains by reducing swimming cost while increasing encounter rates with fast-swimming seals.

Ambient temperature effects on stress-induced hyperthermia in Svalbard ptarmigan.

ABSTRACTStress-induced hyperthermia (SIH) is commonly observed during handling in homeotherms. However, in birds, handling in cold environments typically elicits hypothermia. It is unclear whether this indicates that SIH is differently regulated in this taxon or if it is due to size, because body temperature changes during handling in low temperatures have only been measured in small birds <0.03 kg (that are more likely to suffer high heat loss when handled). We have therefore studied thermal responses to handling stress in the intermediate-sized (0.5–1.0 kg) Svalbard ptarmigan (Lagopus muta hyperborea) in 0°C and −20°C, in winter and spring. Handling caused elevated core body temperature and peripheral vasoconstriction that reduced back skin temperature. Core temperature increased less, and back skin temperature decreased more, in −20°C than in 0°C, probably because of higher heat-loss rate at the lower temperature. Responses were qualitatively consistent between seasons, despite higher body condition/insulation in winter and dramatic seasonal changes in photoperiod, both of which could possibly affect stress responsiveness. Our study supports the notion that SIH is a general thermoregulatory reaction to acute stressors in endotherms, but also suggests that body size and thermal environment should be taken into account when evaluating this response in birds.

Advances in pre-hospital recognition and cooling treatment of exertional heat stroke

Heat stroke (HS) is a life-threatening illness characterized by an altered level of consciousness with an elevated core body temperature 40 centigrade, which may be further classified as exertional heat stroke (EHS) or classical heat stroke (CHS) according to the etiology of the condition. In recent years, the morbidity of EHS increases year by year. The severity and clinical outcome for an EHS casualty have a strong correlation with the area under the time and temperature curve for heat exposure. The early recognition and rapid cooling body core temperature ≤ 38.9 centigrade within 30 minutes of EHS results in the best clinical outcome and minimize severe multiple organ dysfunction and death for patients. Cold water immersion (CWI) is considered as an optimum cooling method for the reversal of hyperthermia in EHS. Some alternative modalities have also shown acceptable cooling rate, for example, the subjects immersed in a circulated water bath controlled below 20 centigrade, tarp-assisted cooling with oscillation, body cooling unit, undressed, air-conditioned room, the whole body and large vessels placed ice packs, massaging the extremities; cold intravenous saline applied to dehydrated one. It is necessary to monitor body core temperature for hypothermia and/or recurrent hyperthermia, and to provide physical care for shivering, agitation, or concerns with the potential discomfort combativeness that may occur during cooling process. In this paper, pre-hospital recognition, care, monitoring and rapid cooling treatment measures of EHS have been reviewed to provide references for early identification of EHS and scientific, reasonable and effective cooling treatment.

Core Body Temperature but Not Intraabdominal Pressure Predicts Postoperative Complications Following Closed-System Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Administration.

Hyperthermic intraperitoneal chemotherapy (HIPEC) following cytoreductive surgery (CRS), performed using closed-abdomen technique (CAT), may affect intraabdominal pressure (IAP). High IAP may increase postoperative complications due to decreased venous return and hypoperfusion to vital organs. Elevated core body temperature (CBT) may cause multiorgan dysfunction. Low IAP or CBT could result in suboptimal HIPEC and potentially translate into early disease recurrence. The aim of the present study is to identify possible correlations between IAP or CBT and postoperative complications. Continuous intraabdominal pressure measurement was performed by intraabdominal catheter. Inflow temperature was set at 44°C, and mean perfusate temperature was 42°C. CBT was measured continuously in the distal esophagus. We compared the rate of postoperative complications between the low IAP group (2-10mmHg, n=28), target IAP group (10-20mmHg, n=71), and high IAP group (20-34mmHg, n=16) as well as with CBT as a continuous variable. 115 patients were included in the study. There was no difference between IAP groups in terms of age, gender, primary diagnosis, operative peritoneal cancer index, CBT, or operative time. There was no correlation between IAP and postoperative complications or with prolonged hospital stay. On multivariate analysis, elevated mean CBT was a positive predictor of postoperative complications (p=0.035). IAP level during closed-abdomen technique HIPEC is not associated with postoperative complications. However, elevated CBT may increase postoperative complications.

Characterization of Mucosal Disaccharidases from Human Intestine.

In this study, we used a brush border membrane (BBM) preparation from human small intestine to analyze the proportion and the activity of major intestinal disaccharidases, including sucrase-isomaltase (SI), maltase-glucoamylase (MGAM) and lactase-phlorizin hydrolase (LPH). SI, MGAM and LPH respectively constituted 8.2%, 2.7% and 1.4% of total BBM protein. The activity of SI and LPH decreased threefold after purification from the brush border membrane, which highlights the effect of membrane microdomains on the functional capacity of these enzymes. All of the disaccharidases showed optimal activity at pH 6, over 50% residual activity between pH 5 to pH 7, and increasing activity with rising temperatures up to 45 °C, along with a stable functional structure. Therefore the enzymes can withstand mild intraluminal pH alterations with adequate function, and are able to increase their activity with elevated core body temperature. Our data provide a functional measure for characterization of intestinal disaccharidases under different physiological and pathological conditions.

Population-based case-control study of the association between weather-related extreme heat events and neural tube defects.

Elevated body core temperature has been shown to have teratogenic effects in animal studies. Our study evaluated the association between weather-related extreme heat events (EHEs) in the summer season and neural tube defects (NTDs), and further investigated whether pregnant women with a high pregestational body mass index (BMI) have a greater risk of having a child with NTDs associated with exposure to EHE than women with a normal BMI. We conducted a population-based case-control study among mothers of infants with NTDs and mothers of infants without major birth defects, who participated in the National Birth Defects Prevention Study and had at least 1 day of the third or fourth week postconception during summer months. EHEs were defined using the 95th and the 90th percentiles of the daily maximum universal apparent temperature. Adjusted odds ratios and 95% confidence intervals were calculated using unconditional logistic regression models with Firth's penalized likelihood method while controlling for other known risk factors. Overall, we did not observe a significant association between EHEs and NTDs. At the climate region level, consistently elevated but not statistically significant estimates were observed for at least 2 consecutive days with daily universal apparent maximum temperature above the 95th percentile of the UATmax distribution for the season, year, and weather monitoring station in New York (Northeast), North Carolina and Georgia (Southeast), and Iowa (Upper Midwest). No effect modification by BMI was observed. EHEs occurring during the relevant developmental window of embryogenesis do not appear to appreciably affect the risk of NTDs. Future studies should refine exposure assessment, and more completely account for maternal activities that may modify the effects of weather exposure. Birth Defects Research 109:1482-1493, 2017.© 2017 Wiley Periodicals, Inc.

Visual function and retinal vessel diameters during hyperthermia in man.

To assess the effect of elevated core body temperature on temporal and spatial contrast sensitivity and retinal vessel diameters. The study included 13 healthy volunteers aged 20-37years. Core body temperature elevation (target +1.1°C) was induced by wrapping the participants in cling film, tinfoil and warming blankets. Subsequent cooling was achieved by undressing. Flicker sensitivity (critical flicker fusion frequency) was chosen to assess temporal resolution, while the Freiburg Vision Test was used to determine spatial contrast sensitivity at 1.5 cycles per degree. Scanning laser ophthalmoscopy was used to measure retinal trunk vessel diameters. Assessment was made at baseline, during hyperthermia and after cooling. The induction of a mean increase in core body temperature of 1.02°C was associated with a 7.15-mmHg mean reduction in systolic blood pressure (p<0.01), a 10.6-mmHg mean reduction in diastolic blood pressure (p<0.01), a mean increase in pulse rate of 36.3bpm (p<0.0001), a 2.66% improvement in flicker sensitivity (CI95 1.37-3.94, p<0.001), a 2.80% increase in retinal artery diameters (CI95 1.09-4.51, p<0.01) and a 2.95% increase in retinal vein diameters (CI95 0.96-4.94, p<0.01). There was no detectable effect of temperature on spatial contrast sensitivity. All ocular test parameters returned to baseline levels after cooling. Increased core body temperature was accompanied by improved temporal visual resolution and retinal trunk vessel dilation. The results suggest that hyperthermia is associated with enhanced retinal function and increased retinal metabolism.

Reverse Engineering the Febrile System.

Fever, the elevation of core body temperature by behavioral or physiological means, is one of the most salient aspects of human sickness, yet there is debate regarding its functional role. In this paper, we demonstrate that the febrile system is an evolved adaptation shaped by natural selection to coordinate the immune system to fight pathogens. First, we show that previous arguments in favor of fever being an adaptation are epistemologically inadequate, and we describe how an adaptationist strategy addresses this issue more effectively. Second, we argue that the mechanisms producing fever provide clear indications of adaptation. Third, we demonstrate that there are many beneficial immune system responses activated during fever and that these responses are not mere byproducts of heat on chemical reactions. Rather, we show that natural selection appears to have modified several immune system effects to be coordinated by fever. Fourth, we argue that there are some adaptations that coordinate the febrile system with other important fitness components, particularly growth and reproduction. Finally, we discuss evidence that the febrile system may also have evolved an antitumor function, providing suggestions for future research into this area. This research informs the debate on the functional value of fever and antipyretic use.

Core Temperature in Service Members With and Without Traumatic Amputations During a Prolonged Endurance Event.

Service members with traumatic amputations may be at an increased risk of elevated core body temperature, since their ability to dissipate heat may decrease with the reduction in body surface area (BSA) after injury. Elevated core temperature can impair physical performance during combat operations potentially putting the service members and their teams at risk. The purpose of this study was to compare core temperature between individuals with and without amputations during a prolonged endurance event. Twenty healthy male military service members (10 with amputations, 10 without) participated in the Bataan Memorial Death March 26.2-mile event on March 27, 2011. Data collected include BSA, body mass index, body composition, body weight before and after the event, core temperature during the event, and postevent hydration status. Body composition was measured by dual-energy X-ray absorptiometry. Body weight was measured by digital scale. Core temperature was measured by ingestible sensor. Hydration was measured by urine specific gravity. The Walter Reed Army Medical Center Institutional Review Board approved this study and participants provided written informed consent. Three participants' data were not included in the analyses. No significant differences in core temperature were found between participants in both groups, and no correlation was found between core temperature and either BSA or hydration status. There was no significant difference in maximal core temperature between the groups (p = 0.27). Nearly all participants (8 control, 6 amputation) reached 38.3°C, the threshold for increased risk of heat exhaustion. No subjects reached 40.0°C, the threshold for increased risk of heat stroke. Time spent above the 38.3°C threshold was not significantly different between groups, but varied widely by participant in relation to the duration of the event. Participants without amputations finished the event faster than participants with amputations (7.9 ± 1.4 vs. 9.6 ± 0.96, p < 0.01), possibly indicating that participants with amputations self-selected a slower pace to attenuate increased core temperature. Until conclusive evidence is accumulated, it is prudent for military leaders, trainers, and military service members to closely monitor this population during physical activity to prevent heat injuries.

The Impact of Central and Peripheral Cyclooxygenase Enzyme Inhibition on Exercise-Induced Elevations in Core Body Temperature.

Exercise increases core body temperature (TC) due to metabolic heat production. However, the exercise-induced release of inflammatory cytokines including interleukin-6 (IL-6) may also contribute to the rise in TC by increasing the hypothalamic temperature set point. This study investigated whether the exercise-induced increase in TC is partly caused by an altered hypothalamic temperature set point. Fifteen healthy, active men age 36 ± 14 y were recruited. Subjects performed submaximal treadmill exercise in 3 randomized test conditions: (1) 400 mg ibuprofen and 1000 mg acetaminophen (IBU/APAP), (2) 1000 mg acetaminophen (APAP), and (3) a control condition (CTRL). Acetaminophen and ibuprofen were used to block the effect of IL-6 at a central and peripheral level, respectively. TC, skin temperature, and heart rate were measured continuously during the submaximal exercise tests. Baseline values of TC, skin temperature, and heart rate did not differ across conditions. Serum IL-6 concentrations increased in all 3 conditions. A significantly lower peak TC was observed in IBU/APAP (38.8°C ± 0.4°C) vs CTRL (39.2°C ± 0.5°C, P = .02) but not in APAP (38.9°C ± 0.4°C) vs CTRL. Similarly, a lower ΔTC was observed in IBU/APAP (1.7°C ± 0.3°C) vs CTRL (2.0°C ± 0.5°C, P < .02) but not in APAP (1.7°C ± 0.5°C) vs CTRL. No differences were observed in skin temperature and heart-rate responses across conditions. The combined administration of acetaminophen and ibuprofen resulted in an attenuated increase in TC during exercise compared with a CTRL. This observation suggests that a prostaglandin-E2-induced elevated hypothalamic temperature set point may contribute to the exercise-induced rise in TC.

Pyrexia: aetiology in the ICU.

Elevation in core body temperature is one of the most frequently detected abnormal signs in patients admitted to adult ICUs, and is associated with increased mortality in select populations of critically ill patients. The definition of an elevated body temperature varies considerably by population and thermometer, and is commonly defined by a temperature of 38.0 °C or greater. Terms such as hyperthermia, pyrexia, and fever are often used interchangeably. However, strictly speaking hyperthermia refers to the elevation in body temperature that occurs without an increase in the hypothalamic set point, such as in response to specific environmental (e.g., heat stroke), pharmacologic (e.g., neuroleptic malignant syndrome), or endocrine (e.g., thyrotoxicosis) stimuli. On the other hand, pyrexia and fever refer to the classical increase in body temperature that occurs in response to a vast list of infectious and noninfectious aetiologies in association with an increase in the hypothalamic set point. In this review, we examine the contemporary literature investigating the incidence and aetiology of pyrexia and hyperthermia among medical and surgical patients admitted to adult ICUs with or without an acute neurological condition. A temperature greater than 41.0 °C, although occasionally observed among patients with infectious or noninfectious pyrexia, is more commonly observed in patients with hyperthermia. Most episodes of pyrexia are due to infections, but incidence estimates of infectious and noninfectious aetiologies are limited by studies with small sample size and inconsistent reporting of noninfectious aetiologies. Pyrexia commonly triggers a full septic work-up, but on its own is a poor predictor of culture-positivity. In order to improve culturing practices, and better guide the diagnostic approach to critically ill patients with pyrexia, additional research is required to provide more robust estimates of the incidence of infectious and noninfectious aetiologies, and their relationship to other clinical features (e.g., leukocytosis). In the meantime, using existing literature, we propose an approach to identifying the aetiology of pyrexia in critically ill adults.

Exertional heat illness: a review of the syndrome affecting racing Thoroughbreds in hot and humid climates.

Metabolic heat produced by Thoroughbred racehorses during racing can rapidly elevate core body temperature (1°C/min). When environmental conditions are hot and humid, the normal physiological cooling mechanisms become ineffective. The heat accumulated may exceed a critical thermal maximum (estimated to be 42°C), which may trigger a complex pathophysiological cascade with potentially lethal consequences. This syndrome has been labelled exertional heat illness (EHI). EHI is described in humans, but has not been well documented in Thoroughbred racehorses. The clinical signs described in racehorses would suggest that the pathophysiological events affecting the central nervous (CNS) and gastrointestinal systems are similar to those described in humans. Clinical signs are progressive and include signs of endotoxaemia and increasing levels of CNS dysfunction. Initially, horses that may be mildly irritable (agitated, randomly kicking out) may progress to unmanageable (disorientation, severe ataxia, falling) and ultimately convulsions, coma and death. Currently, the approach to treatment is largely empirical and involves rapid and effective cooling, administration of drugs to provide sedation, administration of non-steroidal anti-inflammatory drugs to ameliorate the effects of endotoxaemia and glucocorticoids to stabilise cell membranes and reduce the effects of inflammation on the CNS. This review provides an overview of the current knowledge about EHI in Thoroughbred racehorses, suggests a likely pathophysiology of the syndrome in horses based on the current literature on heat illness in humans and horses, and outlines current treatment strategies being used to treat racehorses with clinical signs of EHI.

Lower thermal sensation in normothermic and mildly hyperthermic older adults.

It is important to know how thermal sensation is affected by normal aging under conditions that elevate core body temperature for the prevention of heat-related illness in older people. We assessed whether thermal sensation under conditions of normothermia (NT) and mild hyperthermia (HT) is lowered in older adults. Seventeen younger (23±3years) and 12 older (71±3years) healthy men underwent measurements of the cold and warmth detection thresholds (±0.1°C/s) of their chest and forearm skin, and whole body warmth perception under NT (esophageal temperature, T es, ~36.5°C) and HT (T es, ~37.3°C; lower legs immersed in 42°C water) conditions. Warmth detection threshold at the forearm was increased in older compared with younger participants under both NT (P=0.006) and HT (P=0.004) conditions. In contrast, cold detection threshold at the forearm was decreased in older compared with younger participants under NT (P=0.001) but not HT (P=0.16). Mild hyperthermia decreased cold detection threshold at forearm in younger participants (P=0.001) only. There were no effects of age and condition on warmth and cold detection thresholds at chest. Whole body warmth perception increased during HT compared with NT in both groups (both, P<0.001), and older participants had lower values than the younger group under NT (P=0.001) and HT (P=0.051). Skin warmth detection thresholds at forearm and whole body warmth perception under NT and HT and skin cold detection thresholds at forearm under NT deteriorated with aging.

The impact of exercise-induced core body temperature elevations on coagulation responses.

Exercise induces changes in haemostatic parameters and core body temperature (CBT). We aimed to assess whether exercise-induced elevations in CBT induce pro-thrombotic changes in a dose-dependent manner. Observational study. CBT and haemostatic responses were measured in 62 participants of a 15-km road race at baseline and immediately after finishing. As haemostasis assays are routinely performed at 37°C, we corrected the assay temperature for the individual's actual CBT at baseline and finish in a subgroup of n=25. All subjects (44±11 years, 69% male) completed the race at a speed of 12.1±1.8km/h. CBT increased significantly from 37.6±0.4°C to 39.4±0.8°C (p<0.001). Post-exercise, haemostatic activity was increased, as expressed by accelerated thrombin generation and an attenuated plasmin response. Synchronizing assay temperature to the subjects' actual CBT resulted in additional differences and stronger acceleration of thrombin generation parameters. This study demonstrates that exercise induces a prothrombotic state, which might be partially dependent on the magnitude of the exercise-induced CBT rise. Synchronizing the assay temperature to approximate the subject's CBT is essential to obtain more accurate insight in the haemostatic balance during thermoregulatory challenging situations. Finally, this study shows that short-lasting exposure to a CBT of 41.2°C does not result in clinical symptoms of severe coagulation. We therefore hypothesize that prolonged exposure to a high CBT or an individual-specific CBT threshold needs to be exceeded before derailment of the haemostatic balance occurs.

Matrix assisted transplantation of functional beige adipose tissue

Event Abstract Back to Event Matrix assisted transplantation of functional beige adipose tissue Kevin Tharp1, 2, Amit Jha2, Kevin Healy2 and Andreas Stahl1 1 UC Berkeley, Metabolic Biology, United States 2 UC Berkeley, Bioengineering, United States Introduction: Novel, clinically relevant approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion of brown/beige-adipose tissues that express uncoupling protein 1 (UCP1) and that decouples mitochondrial respiration from ATP synthesis and in turn drastically increases metabolic rates for thermoregulation (heat production)[1],[2]. The transplantation of brown fat in small animal model systems has demonstrated that exogenous brown fat expansion is an effective method to combat metabolic disorders. Expansion and/or stimulation of UCP1-positive adipose has demonstrated physiologically beneficial reductions in circulating glucose and lipids but there are no sources of transplantable brown fat for human therapeutic purposes. To circumvent this barrier, we present a novel cell scaffold technology optimized to induce “browning”, differentiation of white fat progenitor cells into brown fat-like cells[3]. This injectable hyaluronic acid based hydrogel system, termed BAT-MACT (beige adipose tissue – matrix assisted cellular transplant), establishes functional brown fat-like depots in vivo and induces improvements in the metabolic profiles of the recipients. Materials and Methods: We adapted the biophysical properties of hyaluronic acid-based hydrogels[4],[5] to support the differentiation of white fat derived multipotent stem cells (ADMSCs) into lipid accumulating, UCP1 expressing beige adipose tissue. Specifically, two peptides (CGGKAFDITYVRLKF and CGGRKRLQVQLSIRT) were covalently linked to a hyaluronic acid backbone at a molar ratio of 3:1. ADMSCs differentiated into beige adipocytes were suspended in the optimized hyaluronic acid framework, crosslinked with an MMP-13-cleavable peptide (CQPQGLAKC), and injected into recipient mice. The viability of implanted cells and metabolic profiles of the recipients were thoroughly monitored and examined. Results and Discussion: Subcutaneous implantation of ADMSCs within optimized hydrogels resulted in the establishment of distinct UCP1-expressing implants that successfully attracted host vasculature and persisted for several weeks. Importantly, implant recipients demonstrated elevated core body temperature during cold challenges, enhanced respiration rates, improved glucose homeostasis, and reduced weight gain - demonstrating the therapeutic merit of this highly translatable approach. Conclusion: This novel approach is the first truly clinically translatable system to unlock the therapeutic potential of brown fat-like tissue expansion and demonstrates the merit of bioengineered tissues for metabolic therapies. And, unlike the pharmacological browning of white adipose depots, the implantation of bioengineered beige adipose tissues offers a spatially and temporally controlled therapeutic. The BAT-MACT system provides a non-immunogenic platform to expand beige adipose tissue through immobilized synthetic physical cues, which carries a significantly lower risk of off target effects relative to administration of “browning” factors. Additionally, by relying on the trans-differentiation of white fat derived ADMSCs, a highly abundant cell population, there are few limitations on the amount of implantable organoids that can be generated for clinical deployment with the BAT-MACT technology.

Impact of Elevated Core Body Temperature on Attention Networks.

Cognitive function can be impaired after passive heat exposure and with an elevation in core body temperature (Tcore). This study examined the dynamic correlation among passive heat exposure, Tcore, and cognition. We gave the Attention Network Test of alerting, orienting, and executive control to five groups of five young men who were being exposed to a hyperthermic condition (50°C, 40% relative humidity) for 0, 10, 20, 30, or 40 minutes. We used the participants' reaction time, accuracy (correct responses), efficiency (accuracy÷reaction time), and Tcore to estimate optimal curve models for best fit of data. We could not estimate an appropriate curve model for either alerting or orienting with Tcore, change in Tcore, or duration of passive heat exposure. We estimated quadratic models for Tcore and duration (adjusted R=0.752), change in Tcore and duration (0.906), executive control score and duration (0.509), and efficiency of executive control and duration (0.293). We estimated linear models for executive control score and Tcore (0.479), efficiency of executive control and Tcore (0.261), executive control score and change in Tcore (0.279), and efficiency of executive control and change in Tcore (0.262). Different attentional abilities had different sensitivities to thermal stress. Executive control of attention deteriorated linearly with a rise in Tcore within the normal physiologic range, but deteriorated nonlinearly with longer passive heat exposure.

Matrix-Assisted Transplantation of Functional Beige Adipose Tissue.

Novel, clinically relevant, approaches to shift energy balance are urgently needed to combat metabolic disorders such as obesity and diabetes. One promising approach has been the expansion of brown adipose tissues that express uncoupling protein (UCP) 1 and thus can uncouple mitochondrial respiration from ATP synthesis. While expansion of UCP1-expressing adipose depots may be achieved in rodents via genetic and pharmacological manipulations or the transplantation of brown fat depots, these methods are difficult to use for human clinical intervention. We present a novel cell scaffold technology optimized to establish functional brown fat–like depots in vivo. We adapted the biophysical properties of hyaluronic acid–based hydrogels to support the differentiation of white adipose tissue–derived multipotent stem cells (ADMSCs) into lipid-accumulating, UCP1-expressing beige adipose tissue. Subcutaneous implantation of ADMSCs within optimized hydrogels resulted in the establishment of distinct UCP1-expressing implants that successfully attracted host vasculature and persisted for several weeks. Importantly, implant recipients demonstrated elevated core body temperature during cold challenges, enhanced respiration rates, improved glucose homeostasis, and reduced weight gain, demonstrating the therapeutic merit of this highly translatable approach. This novel approach is the first truly clinically translatable system to unlock the therapeutic potential of brown fat–like tissue expansion.

Maternal separation increases methamphetamine-induced damage in the striatum in male, but not female rats

Methamphetamine abuse impacts the global economy through costs associated with drug enforcement, emergency room visits, and treatment. Previous research has demonstrated early life stress, such as childhood abuse, increases the likelihood of developing a substance abuse disorder. However, the effects of early life stress on neuronal damage induced by binge methamphetamine administration are unknown. We aimed to elucidate the effects of early life stress on methamphetamine induced dopamine damage in the striatum. Pups were separated from dams for 3h per day during the first two weeks of development or 15min for control. In adulthood, rats received either subcutaneous 0.9% saline or 5.0mg/kg METH injections every 2h for a total of four injections. Rectal temperatures were taken before the first injection and 1h after each subsequent injection. Seven days after treatment, rats were euthanized and striatum was collected for quantification of tyrosine hydroxylase (TH) and dopamine transporters (DAT) content by Western blot. Methamphetamine significantly elevated core body temperature in males and decreased striatal DAT and TH content, and this effect was potentiated by early life stress. Females did not exhibit elevated core body temperatures or changes in DAT or TH in either condition. Results indicate maternal separation increases methamphetamine induced damage, and females are less susceptible to methamphetamine induced damage.

Housing temperature influences the pattern of heat shock protein induction in mice following mild whole body hyperthermia

Purpose: Researchers studying the murine response to stress generally use mice housed under standard, nationally mandated conditions as controls. Few investigators are concerned whether basic physical aspects of mouse housing could be an additional source of stress, capable of influencing the subsequent impact of an experimentally applied stressor. We have recently become aware of the potential for housing conditions to impact important physiological and immunological properties in mice.Materials and methods: Here we sought to determine whether housing mice at standard temperature (ST; 22 °C) vs. thermoneutral temperature (TT; 30 °C) influences baseline expression of heat shock proteins (HSPs) and their typical induction following a whole body heating.Results: There were no significant differences in baseline expression of HSPs at ST and TT. However, in several cases, the induction of Hsp70, Hsp110 and Hsp90 in tissues of mice maintained at ST was greater than at TT following 6 h of heating (which elevated core body temperature to 39.5 °C). This loss of HSP induction was also seen when mice housed at ST were treated with propranolol, a β-adrenergic receptor antagonist, used clinically to treat hypertension and stress.Conclusions: Taken together, these data show that housing temperature significantly influences the expression of HSPs in mice after whole body heating and thus should be considered when stress responses are studied in mice.