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Heat shock proteins (HSPs) are induced in response to stressful stimuli and play an important role in cell repair and protection. This study, using immunohistochemistry, aimed to determine whether HSPs are induced in the cerebellum of rats subjected to hyperthermia during postnatal development (PND). The results showed that unlike HSP27 and HSP70, HSP60 and HSP90 were constitutively expressed in the cerebellum of rats. However, hyperthermia induced HSP27 in the white matter (WM) and HSP70 in the Bergmann glial cells, the internal granule layer (IGL), and the WM. In the WM, HSP27 induction was only observed on days PND20, PND25, and PND30, and HSP27 expression was higher on day PND30 compared with days PND20 and PND25 (p < 0.001). In the Bergmann glial cells, HSP70 induction was only observed on days PND5, PND10, and PND20, and HSP70 expression was greater on days PND5 and PND10 compared with day PND20 (p < 0.001). In the IGL and the WM, HSP70 expression was higher on days PND20, PND25, and PND30 compared with days PND5 and PND10 (p < 0.001). These findings indicate that unlike HSP60 and HSP90, HSP27 and HSP70 have different expression patterns in the cerebellum of rats after hyperthermia during PND., Competing Interests: Conflict of Interest: There is no conflict of interest between the authors. All authors have read and approved this article., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Caffeine, a methylxanthine alkaloid, works as a nonselective adenosine receptor antagonist. It is the most widely used psychostimulant drug worldwide. However, caffeine overdose can lead to acute intoxication, posing a clinical problem. Hyperthermia and hyperactivity are associated issues with acute caffeine intoxication; however, no definitive treatment exists. This study aimed to assess the ability of risperidone to attenuate caffeine-induced hyperthermia and hyperactivity while elucidating the unknown mechanisms of caffeine intoxication. The rats received intraperitoneal injections of saline, risperidone (0.25 mg/kg, 0.5 mg/kg), WAY-100635, ketanserin, haloperidol, sulpiride, or SCH 23390, 5 min after the administration of caffeine (25 mg/kg). Subcutaneous temperature and activity counts were measured using nano tag ® for up to 90 min. In vivo microdialysis was used to determine the effect of risperidone on caffeine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline (NA) concentrations in the anterior hypothalamus. Rats were injected with caffeine (25 mg/kg), followed by saline or risperidone (0.5 mg/kg) 5 min later. The levels of DA, 5-HT, and noradrenaline were measured every 15 min for up to 90 min after caffeine administration. Risperidone and 5-HT2A receptor antagonist ketanserin attenuated caffeine-induced hyperthermia and hyperactivity. Haloperidol and dopamine D1 antagonist SCH-23390 exacerbated hyperthermia without any effect on the hyperactivity. In the microdialysis study, risperidone treatment further attenuated caffeine-induced 5-HT elevation, but not DA and NA. Our results indicate that risperidone attenuates caffeine-induced hyperthermia and hyperactivity by blocking 5-HT2A receptor activity and may be potentially useful for treating caffeine intoxication., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A real-time hypothermia and hyperthermia monitoring system with a simple body sensor based on a Convolutional Neural Network (CNN) is presented. The sensor is produced with 3D-printed thermochromic material. Due to the color change feature of thermochromic materials with temperature, 3D-printed thermochromic Polylactic Acid (PLA) material was used to monitor temperature changes visually. In this paper, we have used the transfer learning technique and fine-tuned the AlexNet CNN. Thirty images for each temperature class between 28-44°C and 510 image data were used in the algorithm. We used 80% and 20% of the data for training and validation. We achieved 96.1% accuracy of validation with a fine-tuned AlexNet CNN. The material's characteristics suggest that it could be employed in delicate temperature sensing and monitoring applications, particularly for hypothermia and hyperthermia., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hyperthermia induced by phenethylamines, such as 3,4-methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia., (© 2024. The Author(s).)

Background: The intraoperative use of tourniquets is associated with several complications, including hyperthermia. We present the first documented case of tourniquet-induced hyperthermia in a pediatric patient at our institution., Case: A 5-year-old female with no past medical history underwent tendon release surgery for congenital talipes equinovarus under general anesthesia. Following inflation of a pneumatic tourniquet to a pressure of 250 mmHg on her left thigh, the patient experienced a gradual increase in body temperature. Despite the implementation of cooling measures, the temperature continued to increase until it plateaued. The hyperthermia gradually resolved upon deflation of the tourniquet., Conclusions: Tourniquet-induced hyperthermia should be considered as a potential cause of intraoperative hyperthermia, particularly in the absence of typical signs of malignant hyperthermia. Early recognition and appropriate management, including deflation of the tourniquet and implementation of cooling measures, are crucial for preventing potential complications associated with hyperthermia.

Cholecystokinin (CCK) increases core body temperature via CCK 2 receptors when administered intracerebroventricularly (icv). The mechanisms of CCK-induced hyperthermia are unknown, and it is also unknown whether CCK contributes to the fever response to systemic inflammation. We studied the interaction between central CCK signaling and the cyclooxygenase (COX) pathway. Body temperature was measured in adult male Wistar rats pretreated with intraperitoneal infusion of the nonselective COX enzyme inhibitor metamizol (120 mg/kg) or a selective COX-2 inhibitor, meloxicam, or etoricoxib (10 mg/kg for both) and, 30 min later, treated with intracerebroventricular CCK (1.7 µg/kg). In separate experiments, CCK-induced neuronal activation (with and without COX inhibition) was studied in thermoregulation- and feeding-related nuclei with c-Fos immunohistochemistry. CCK increased body temperature by ∼0.4°C from 10 min postinfusion, which was attenuated by metamizol. CCK reduced the number of c-Fos-positive cells in the median preoptic area (by ∼70%) but increased it in the dorsal hypothalamic area and in the rostral raphe pallidus (by ∼50% in both); all these changes were completely blocked with metamizol. In contrast, CCK-induced satiety and neuronal activation in the ventromedial hypothalamus were not influenced by metamizol. CCK-induced hyperthermia was also completely blocked with both selective COX-2 inhibitors studied. Finally, the CCK 2 receptor antagonist YM022 (10 µg/kg icv) attenuated the late phases of fever induced by bacterial lipopolysaccharide (10 µg/kg; intravenously). We conclude that centrally administered CCK causes hyperthermia through changes in the activity of "classical" thermoeffector pathways and that the activation of COX-2 is required for the development of this response. NEW & NOTEWORTHY An association between central cholecystokinin signaling and the cyclooxygenase-prostaglandin E pathway has been proposed but remained poorly understood. We show that the hyperthermic response to the central administration of cholecystokinin alters the neuronal activity within efferent thermoeffector pathways and that these effects are fully blocked by the inhibition of cyclooxygenase. We also show that the activation of cyclooxygenase-2 is required for the hyperthermic effect of cholecystokinin and that cholecystokinin is a modulator of endotoxin-induced fever.

Although MDMA (ecstasy) is a relatively safe recreational drug and is currently considered for therapeutic use for the treatment of posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD), recreational MDMA use occasionally elicits hyperthermia and hyponatremia, sometimes with a fatal outcome. Specific risk factors for both adverse effects are profuse sweating while vigorously dancing under unfavorable conditions such as high ambient temperatures and insufficient fluid suppletion which result in dehydration. Concomitant use of MDMA and alcohol is highly prevalent, but adds to the existing risk, because alcohol facilitates the emergence of MDMA-induced adverse events, like hyperthermia, dehydration, and hyponatremia. Because of potential health-related consequences of concomitant use of MDMA and alcohol, it is important to identify the mechanisms of the interactions between alcohol and MDMA. This review summarizes the main drivers of MDMA-induced hyperthermia, dehydration, and hyponatremia and the role of concomitant alcohol use. It is shown that alcohol use has a profound negative impact by its interaction with most of these drivers, including poikilothermia, exposure to high ambient temperatures, heavy exercise (vigorous dancing), vasoconstriction, dehydration, and delayed initiation of sweating and diuresis. It is concluded that recreational and clinical MDMA-users should refrain from concomitant drinking of alcoholic beverages to reduce the risk for adverse health incidents when using MDMA., (© 2021. The Author(s).)

Hyperthermia and exertional heat illness increase gastrointestinal (GI) permeability, although whether the latter is only via hyperthermia is unclear. The aim of this pilot study was to determine whether different changes in GI permeability, characterized by an increased plasma lactulose:rhamnose concentration ratio ([L:R]), occurred in exercise hyperthermia in comparison to equivalent passive hyperthermia. Six healthy adult male participants (age 25 ± 5 years, mass 77.0 ± 6.7 kg, height 181 ± 6 cm, peak oxygen uptake [ V · O 2 peak ] 48 ± 8 ml.kg -1 .min -1 ) underwent exercise under hot conditions (Ex-Heat) and passive heating during hot water immersion (HWI). Heart rate (HR), rectal temperature (T CORE ), rating of perceived exertion (RPE), and whole-body sweat loss (WBSL) were recorded throughout the trials. The L:R ratio, peak HR, change in HR, and change in RPE were higher in Ex-Heat than HWI, despite no differences in trial duration, peak core temperature or WBSL. L:R was strongly correlated (p < 0.05) with HR peak (r = 0.626) and change in HR (r = 0.615) but no other variable. The greater L:R in Ex-Heat, despite equal T CORE responses to HWI, indicates that increased cardiovascular strain occurred during exercise, and exacerbates hyperthermia-induced GI permeability at the same absolute temperature., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: We investigated the therapeutic effect of targeting extracellular vesicles (EVs) loaded with indocyanine green (ICG) and paclitaxel (PTX) on glioma., Methods: Raw264.7 cells were harvested to extract EVs for the preparation of ICG/PTX@RGE-EV by electroporation and click chemistry. We evaluated the success of modifying Neuropilin-1 targeting peptide (RGE) on the EV membrane of ICG/PTX@RGE-EV using super-resolution fluorescence microscopy and flow cytometry. Spectrophotometry and high performance liquid chromatography (HPLC) were implemented for qualitative and quantitative analysis of the ICG and PTX loaded in EVs. Photothermal properties of the vesicles were evaluated by exposing to 808-nm laser light. Western blot analysis, cell counting kit 8 (CCK-8), Calcein Acetoxymethyl Ester/propidium iodide (Calcein-AM/PI) staining, and flow cytometry were utilized for assessing effects of vesicle treatment on cellular behaviors. A nude mouse model bearing glioma was established to test the targeting ability and anti-tumor action of ICG/PTX@RGE-EV in vivo., Results: Under exposure to 808-nm laser light, ICG/PTX@RGE-EV showed good photothermal properties and promotion of PTX release from EVs. ICG/PTX@RGE-EV effectively targeted U251 cells, with activation of the Caspase-3 pathway and elevated apoptosis in U251 cells through chemotherapy combined with hyperthermia. The anti-tumor function of ICG/PTX@RGE-EV was confirmed in the glioma mice via increased accumulation of PTX in the ICG/PTX@RGE-EV group and an increased median survival of 48 days in the ICG/PTX@RGE-EV group as compared to 25 days in the PBS group., Conclusion: ICG/PTX@RGE-EV might actively target glioma to repress tumor growth by accelerating glioma cell apoptosis through combined chemotherapy-hyperthermia., (© 2021. The Author(s).)

Background: Hyperthermia, induced by exercise in the heat, alters the redox status. The physiological significance of these observations remains uncertain but may justify why the consequences of exercising in the heat span from positive health adaptations to negative and even lethal outcomes. Here, we conducted a systematic review to investigate the redox responses during acute exercise in the heat in healthy adults., Methods: We searched MEDLINE, Cochrane Wiley, ClinicalTrials.gov, PEDRO and LILACS for clinical trials investigating pro- and antioxidant responses to exercise associated with hyperthermia and/or sweat-induced dehydration in healthy young individuals. Two independent reviewers extracted data and assessed the quality of the included studies., Results: A total of 1,014 records were selected, nine full papers were evaluated for eligibility, and eight studies met the inclusion criteria. Overall, results show that hyperthermia promotes oxidative stress both at the tissue level and in the circulation. Exercising in the heat heightens endogenous antioxidant defense systems, attenuating the negative effects of hyperthermia on oxidative damage. Studies also indicate that sweat-induced dehydration promotes oxidative stress, which is attenuated by rehydration., Conclusion: These findings suggest that changes in redox status play a role in determining whether an acute bout of exercise in the heat lead to adaptive or maladaptive outcomes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: As a ClinGen Expert Panel (EP) we set out to adapt the American College of Medical Genetics and Genomics (ACMG)/Association for Molecular Pathology (AMP) pathogenicity criteria for classification of RYR1 variants as related to autosomal dominantly inherited malignant hyperthermia (MH)., Methods: We specified ACMG/AMP criteria for variant classification for RYR1 and MH. Proposed rules were piloted on 84 variants. We applied quantitative evidence calibration for several criteria using likelihood ratios based on the Bayesian framework., Results: Seven ACMG/AMP criteria were adopted without changes, nine were adopted with RYR1-specific modifications, and ten were dropped. The in silico (PP3 and BP4) and hotspot criteria (PM1) were evaluated quantitatively. REVEL gave an odds ratio (OR) of 23:1 for PP3 and 14:1 for BP4 using trichotomized cutoffs of ≥0.85 (pathogenic) and ≤0.5 (benign). The PM1 hotspot criterion had an OR of 24:1. PP3 and PM1 were implemented at moderate strength. Applying the revised ACMG/AMP criteria to 44 recognized MH variants, 29 were classified as pathogenic, 13 as likely pathogenic, and 2 as variants of uncertain significance., Conclusion: Curation of these variants will facilitate classification of RYR1/MH genomic testing results, which is especially important for secondary findings analyses. Our approach to quantitatively calibrating criteria is generalizable to other variant curation expert panels.

Immune checkpoint inhibitors (ICIs) have achieved prominent efficacy in the treatment of numerous cancers, which is the most significant breakthrough in cancer therapy in recent years. However, ICIs are associated with a series of immune-related adverse events (irAEs). Pneumonitis is an uncommon but potentially fatal irAE. In the case reported here, a patient with advanced small cell lung cancer (SCLC) had rapid progression of disease following chemotherapy and received ICIs. The patient experienced severe immune-related hyperthermia followed by immune-related pneumonitis. Fortunately, a good clinical response was achieved after the patient received corticosteroids and tocilizumab., (© 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

It is unclear whether men and women perceive thermal stress differently when changes in intestinal temperature (ΔTin) and metabolic heat production (MHprod) are matched between sexes during exercise hyperthermia. This study tested the hypothesis that females have enhanced sensitivity to comfort and perception of thermal stress during exercise hyperthermia in these conditions. We had 22 healthy active adults (11 males, 11 females; M age = 22.4 years, SD  = 4.9 ; M height = 169 cm, SD  = 7.6; M weight = 68.3 kg, SD  = 13) exercise in random order, separated by at least three days at similar MHprod ( M  = 7.0 W/kg, SD  = 1.5; p  = 0.32) for 60 minutes on a cycle ergometer in cool ( M  = 24.0 0 C, SD  = 0.0; M  = 14.4%Rh, SD  = 3.6) and hot ( M  = 42.3°C, SD  = 0.2; M  = 10-60%Rh) environments with a progressive increase in humidity conditions. We measured ΔTin, and thermal stress indices for sensation (TS), comfort (TC), pleasantness (TP), and stickiness (S), feeling (FS scale), stress (visual analogue stress scale, VAS), focus (F) and felt arousal (FAS scale). We examined environmental conditions as wet bulb globe temperatures (WBGT). Males and females had similar increases in ΔTin (ME: WBGT; p  < 0.0001), and both groups reported increased TS and TC and decreased TP (ME: WBGT, p  ≤ 0.01). However, females reported that TS, TC, and TP, felt hotter overall, more uncomfortable, and more unpleasant, compared to males (ME: Sex; p  < 0.04). Overall, females felt worse and were more stressed compared to males (ME: Sex; p ≤ 0.05). Females also reported greater internal focus as WBGT increased compared to males (I: WBGT × Sex; p  < 0.003). Knowing that females perceive thermal stress during exercise hyperthermia to be hotter, more uncomfortable, more unpleasant, and more stressful compared to males can help coaches/trainers plan different exercise routines for exercisers of both sexes.

Background: Immunotherapy has profoundly changed the landscape of cancer management and represented the most significant breakthrough. Yet, it is a formidable challenge that the majority of cancers - the so-called "cold" tumors - poorly respond to immunotherapy. To find a general immunoregulatory modality that can be applied to a broad spectrum of cancers is an urgent need. Methods: Magnetic hyperthermia (MHT) possesses promise in cancer therapy. We develop a safe and effective therapeutic strategy by using magnetism-mediated targeting MHT-immunotherapy in "cold" colon cancer. A magnetic liposomal system modified with cell-penetrating TAT peptide was developed for targeted delivery of a CSF1R inhibitor (BLZ945), which can block the CSF1-CSF1R pathway and reduce M2 macrophages. The targeted delivery strategy is characterized by its magnetic navigation and TAT-promoting intratumoral penetration. Results: The liposomes (termed TAT-BLZmlips) can induce ICD and cause excessive CRT exposure on the cell surface, which transmits an "eat-me" signal to DCs to elicit immunity. The combination of MHT and BLZ945 can repolarize M2 macrophages in the tumor microenvironment to relieve immunosuppression, normalize the tumor blood vessels, and promote T-lymphocyte infiltration. The antitumor effector CD8 + T cells were increased after treatment. Conclusion: This work demonstrated that TAT-BLZmlips with magnetic navigation and MHT can remodel tumor microenvironment and activate immune responses and memory, thus inhibiting tumor growth and recurrence., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Exercise often causes skeletal muscle hyperthermia, likely resulting in decreased efficiency of mitochondrial respiration. We hypothesized that athletic conditioning would improve mitochondrial tolerance to hyperthermia. Skeletal muscle biopsies were obtained from six Alaskan sled dogs under light general anesthesia before and after a full season of conditioning and racing, and respiration of permeabilized muscle fibers was measured at 38, 40, 42, and 44°C. There was no effect of temperature on phosphorylating respiration, and athletic conditioning increased maximal phosphorylating respiration by 19%. Leak respiration increased and calculated efficiency of oxidative phosphorylation decreased with increasing incubation temperature, and athletic conditioning resulted in higher leak respiration and lower calculated oxidative phosphorylation efficiency at all temperatures. Conditioning increased skeletal muscle expression of putative mitochondrial leak pathways adenine nucleotide transporter 1 and uncoupling protein 3, both of which were correlated with the magnitude of leak respiration. We conclude that athletic conditioning in elite canine endurance athletes results in increased capacity for mitochondrial proton leak that potentially reduces maximal mitochondrial membrane potential during periods of high oxidative phosphorylation. This effect may provide a mechanistic explanation for previously reported decreases in exercise-induced muscle damage in well-conditioned subjects. NEW & NOTEWORTHY Athletic conditioning is expected to increase exercise capacity through improved function of cardiopulmonary and musculoskeletal tissues. Our finding of decreased calculated efficiency of skeletal muscle mitochondria in one of the premier mammalian athletes suggests that this mandate for improved function may take the form of sacrificing capacity for maximal oxidative phosphorylation to minimize exercise-induced muscle damage caused by mitochondrial oxidative stress.

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 β 3 adrenergic receptor (β 3 AR) 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 β 3 AR, 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 β 3 AR/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 β 3 AR/BAT. We found that OTR-mediated temperature elevation is largely responsible for SH during social interaction in mice-albeit not substantially via β 3 AR-dependent BAT thermogenesis. Further, our results reveal a complex relationship between OTR, β 3 AR, 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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Intra-operative hypothermia has been extensively investigated. However, the incidence of intra-operative hyperthermia has not been investigated in detail., Objective: The main objective of this study was to assess the incidence and risk factors of new-onset intra-operative hyperthermia in a large surgical patient population., Design: Retrospective database review., Setting: Tertiary-care teaching hospital., Patients: Patients undergoing surgery with general anaesthesia between 1 January 2002 and 31 December 2017 were included., Main Outcome Measures: The primary outcome measurement was new-onset intra-operative hyperthermia (>37.5 °C). A logistic regression model was fitted to identify risk factors for intra-operative hyperthermia., Results: A total of 103 648 patients were included in the final analyses. The incidence of new-onset hyperthermia in the overall patient cohort was 6.45%, reaching 20 to 30% after prolonged (>8 h) surgery, and was up to 26.5% in paediatric patients. The use of forced air active patient warming, larger amounts of fluid administration, longer surgery, younger age and smaller body size were all independently associated with intra-operative hyperthermia. The adoption of the Surgical Care Improvement Project (SCIP) temperature measures was associated with an increased incidence of intra-operative hyperthermia., Conclusion: Mild intra-operative hyperthermia is not uncommon particularly in longer procedures and small children., (Copyright © 2020 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Liver fibrosis is a major health problem with multiple associated complications, which, to date, has no effective treatment. Hepatic stellate cells are the main responsible cells for fibrosis formation; upon their activation, excess accumulation of extracellular matrix and collagen deposits occurs. The mitogen platelet-derived growth factor (PDGF) and its receptor β (PDGFRβ) play a major role in hepatic stellate cells activation and are, therefore, promising targets for antifibrotic therapies. Gold nanorods hold great potential for diseased liver treatments, since their passive hepatic accumulation enhances active targeting strategies, hence increasing therapeutic efficiency. In addition, gold nanorods have photothermal properties that, combined with specific cell delivery, can be exploited to induce localized near-infrared light-mediated thermal ablation. Here, we demonstrate that gold nanorods coated with anti-PDGFRβ specifically target activated hepatic stellate cells in vivo . Additionally, gold nanorods-PDGFRβ-mediated photothermal therapy decreases fibrosis, hepatic inflammation, and hepatocyte injury in the experimental model of CCl 4 -induced liver fibrosis in mice.

Tristetraprolin (TTP), an RNA-binding protein, controls the stability of RNA by capturing AU-rich elements on their target genes. It has recently been identified that TTP serves as an anti-inflammatory protein by guiding the unstable mRNAs of pro-inflammatory proteins in multiple cells. However, it has not yet been investigated whether TTP affects the inflammatory responses in the hypothalamus. Since hypothalamic inflammation is tightly coupled to the disturbance of energy homeostasis, we designed the current study to investigate whether TTP regulates hypothalamic inflammation and thereby affects energy metabolism by utilizing TTP-deficient mice. We observed that deficiency of TTP led to enhanced hypothalamic inflammation via stimulation of a variety of pro-inflammatory genes. In addition, microglial activation occurred in the hypothalamus, which was accompanied by an enhanced inflammatory response. In line with these molecular and cellular observations, we finally confirmed that deficiency of TTP results in elevated core body temperature and energy expenditure. Taken together, our findings unmask novel roles of hypothalamic TTP on energy metabolism, which is linked to inflammatory responses in hypothalamic microglial cells.

We present a case of a 64-year-old woman who developed severe non-exertional hyperthermia (NEHT) due to excessive anticholinergic effects from her psychiatric medications. The patient was found unresponsive in a non-air-conditioned room where the outside temperature was over 33°C. She presented with altered mental status, hypotension and an oral temperature of 42°C. Drug-drug interactions from her home medications for depression, bipolar disorder and seizures (amitriptyline, cyclobenzaprine, benztropine, topiramate, clonazepam, trazodone) were suspected. Blood cultures grew Staphylococcus hominis The patient quickly returned to baseline with supportive care in the intensive care unit. She was treated for the Staph hominis bacteraemia with a 7-day course of vancomycin. Due to her quick recovery and lack of neurological findings, severe NEHT with associated bacteraemia was determined to have caused her presenting symptoms. This patient's multiple anticholinergic medications increased her susceptibility to develop NEHT by inhibited sweating, this patient's natural cooling mechanism., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This study demonstrates the rational fabrication of a magnetic composite nanofiber mesh that can achieve mutual synergy of hyperthermia, chemotherapy, and thermo-molecularly targeted therapy for highly potent therapeutic effects. The nanofiber is composed of biodegradable poly(ε-caprolactone) with doxorubicin, magnetic nanoparticles, and 17-allylamino-17-demethoxygeldanamycin. The nanofiber exhibits distinct hyperthermia, owing to the presence of magnetic nanoparticles upon exposure of the mesh to an alternating magnetic field, which causes heat-induced cell killing as well as enhanced chemotherapeutic efficiency of doxorubicin. The effectiveness of hyperthermia is further enhanced through the inhibition of heat shock protein activity after hyperthermia by releasing the inhibitor 17-allylamino-17-demethoxygeldanamycin. These findings represent a smart nanofiber system for potent cancer therapy and may provide a new approach for the development of localized medication delivery.

Hyperthermia produces profound redistribution of blood and circulatory reflex function. We investigated the potential for lower body positive pressure (LBPP) to maintain or restore haemodynamics during graded hyperthermia. Eight healthy adults rested supine in a custom-made LBPP box, sealed distal to the iliac crest. Following 5 min of normothermic rest, 20 mmHg of LBPP was applied and repeated when core temperature (T core ) had increased passively by +0.5 and +1°C. Primary dependent variables included mean middle cerebral artery blood velocity (MCAv mean , transcranial Doppler), mean arterial blood pressure (MAP, finger photoplethysmography), heart rate (HR) and partial pressure of end-tidal carbon dioxide (P ET CO 2 ). The absolute increase in MAP during LBPP was lower at T core +1°C (2 ± 3 mmHg), compared with normothermia (7 ± 3 p = .01). The modest increase in MCAv mean was unchanged by T core (normothermia, 2 ± 3 cm/s; +0.5°C, 3 ± 3 cm/s and +1°C, 3 ± 4 cm/s, p = .74). By design, P ET CO 2 was unchanged in all conditions from normothermic baseline (42 ± 1, p = .81). LBPP-induced changes in HR were greater at +0.5°C (-13 ± 4 b/min) and +1°C (-12 ± 6 b/min) compared with normothermia (-3 ± 3 b/min, p = .01 and p = .01, respectively). These data indicate that despite a significant attenuation in MAP to LBPP with moderate hyperthermia, MCAv mean dynamics were unchanged among the thermal manipulations., (© 2020 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Arginine vasopressin (AVP) is a neuropeptide acting as a neuromodulator in the brain and plays multiple roles, including a thermoregulatory one. However, the cellular mechanisms of action are not fully understood. Carried out are patch clamp recordings and calcium imaging combined with pharmacological tools and single-cell RT-PCR to dissect the signaling mechanisms activated by AVP. Optogenetics combined with patch-clamp recordings were used to determine the neurochemical nature of these neurons. Also used is telemetry combined with chemogenetics to study the effect of activation of AVP neurons in thermoregulatory mechanisms. This article reports that AVP neurons in the medial preoptic (MPO) area release GABA and display thermosensitive firing activity. Their optogenetic stimulation results in a decrease of the firing rates of MPO pituitary adenylate cyclase-activating polypeptide (PACAP) neurons. Local application of AVP potently modulates the synaptic inputs of PACAP neurons, by activating neuronal AVPr1a receptors and astrocytic AVPr1b receptors. Chemogenetic activation of MPO AVP neurons induces hyperthermia. Chemogenetic activation of all AVP neurons in the brain similarly induces hyperthermia and, in addition, decreases the endotoxin activated fever as well as the stress-induced hyperthermia., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Epidural analgesia is associated with intrapartum hyperthermia, and chorioamnionitis is associated with neonatal brain injury. However, it is not known if epidural hyperthermia is associated with neonatal brain injury. This systematic review and meta-analysis investigated three questions: (1) does epidural analgesia cause intrapartum hyperthermia, (2) is intrapartum hyperthermia associated with neonatal brain injury, and (3) is epidural-induced hyperthermia associated with neonatal brain injury?, Methods: PubMed, ISI Web of Knowledge, The Cochrane Library, and Embase were searched from inception to January 2020 using Medical Subject Headings (MeSH) terms relating to epidural analgesia, hyperthermia, labour, and neonatal brain injury. Studies were reviewed independently for inclusion and quality by two authors (Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach). Two meta-analyses were performed using the Mantel-Haenszel fixed effect method to generate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Forty-one studies were included for Question 1 (646 296 participants), 36 for Question 2 (11 866 021 participants), and two studies for Question 3 (297 113 participants). When the mode of analgesia was randomised, epidural analgesia was associated with intrapartum hyperthermia (OR: 4.21; 95% CI: 3.48-5.09). There was an association between intrapartum hyperthermia and neonatal brain injury (OR: 2.79; 95% CI: 2.54-2.3.06). It was not possible to quantify the association between epidural-induced hyperthermia and neonatal brain injury., Conclusions: Epidural analgesia is a cause of intrapartum hyperthermia, and intrapartum hyperthermia of any cause is associated with neonatal brain injury. Further work is required to establish if epidural-induced hyperthermia is a cause of neonatal brain injury., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

The physiology of hyperthermia or heat stress in mammals is complex. It is a totally systemic condition that in varying degrees involves all organs, tissues and body fluid compartments. The nature and magnitude of the response is influenced by animal specific characteristics (e.g. age, diet, body condition, gender, reproductive stage), environment and animal management. Given the multifaceted nature of heat stress, and the varied ruminant production systems based in varied geoclimatic zones, it has been difficult to find appropriate measures of heat stress for production ruminants. This has become an urgent challenge as production systems intensify globally in a warming climate. Bioclimatic indices such as the Temperature-Humidity Index (THI) have evolved to incorporate some measure of animal physiology. However, these indices do not have strong relationships with core temperature trajectories and altered respiratory dynamics of animals with excessive heat load. In recent decades, the careful physiology studies of the 1950-80s, have given way to numerous studies trialling a plethora of new technologies and computational approached to measure heat stress. Infrared thermography of body surface temperatures, automated measures of respiration rate and radiotelemetry of internal body temperatures are the most intensively researched. The common goal has been to find the 'holy grail' decision-making threshold or timepoint as to the animal's wellbeing. Are we making any progress?, (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

The present study aimed to determine the effect of hyperthermia on both electrochemical and mechanical components of the electromechanical delay (EMD), using very-high-frame-rate ultrasound. Electrically evoked peak twitch force, EMD, electrochemical (D m ; i.e., delay between stimulation and muscle fascicle motion), and mechanical (T m ; i.e., delay between fascicle motion and force production onset) components of EMD were assessed in 16 participants. Assessments were conducted in a control ambient environment (CON; 26°C, 34% relative humidity) and in a hot ambient environment (HOT; 46-50°C, 18% relative humidity, after ∼127 min of heat exposure). Following heat exposure, gastrocnemius medialis temperature was 37.0 ± 0.6°C in HOT vs. 34.0 ± 0.8°C in CON ( P < 0.001). EMD was shorter (9.4 ± 0.8 ms) in HOT than in CON (10.8 ± 0.6 ms, P < 0.001). Electrochemical processes were shorter in HOT than in CON (4.0 ± 0.8 ms vs. 5.5 ± 0.9 ms, respectively, P < 0.001), whereas mechanical processes were unchanged ( P = 0.622). These results demonstrate that hyperthermia reduces electromechanical delay via accelerated electrochemical processes, whereas force transmission along the active and passive parts of the series elastic component is not affected following heat exposure. The present study demonstrates that heat exposure accelerates muscle contraction thanks to faster electrochemical processes. Further investigations during voluntary contractions would contribute to better understand how these findings translate into motor performance. NEW & NOTEWORTHY Hyperthermia (targeted core temperature: 38.5°C) reduces the time between gastrocnemius medialis stimulation and the onset of plantar flexor force production in vivo. This reduction in electromechanical delay is concomitant to an earlier motion of muscle fascicle compared with thermoneutral environment. However, hyperthermia has no impact on the duration of force transmission along aponeurosis and tendon, thereby reflecting different effects of heat exposure on contractile and elastic properties of the muscle-tendon unit.

In recent years, the exploitation of magnetic nanoparticles in smart polymeric matrices have received increased attention in several fields as site-specific drug delivery systems. Here, ultrasonic-assisted emulsion copolymerization of N -isopropylacrylamide (NIPAM) and 2-(N,N-diethylaminoethyl) methacrylate (DEAEMA) in the presence of Fe 3 O 4 nanoparticles was employed to prepare pH- and temperature-responsive magnetite nanocomposite particles (MNCPs). The obtained MNCPs were fully characterized by TEM, DSC, FT-IR, VSM, and XRD techniques. They had an average particle size of 70 nm with a lower critical solution temperature of 42 °C and superparamagnetic properties. In addition, MNCPs were loaded with methotrexate (MTX) as an anticancer drug, and their in vitro drug release was studied in different pH values and temperatures and in the presence of an alternating magnetic field. Noteworthy that the highest rate of MTX release was observed at pH 5.5 and 42 °C. Cell viability of the treated MCF-7 human breast cancer cell line with free MTX, MNCPs, and MTX-loaded MNCPs or in combination with magnetic hyperthermia (MHT) and water-based hyperthermia was comparatively studied. The obtained results showed about 17% higher antiproliferative activity for the MTX-loaded MNCPs accompanied by MHT relative to that of free MTX.

Introduction: Defining extreme temperatures as the cause of death remains challenging. It is mostly based on circumstantial, macroscopic and microscopic features., Methods: We retrospectively compared groups of cases of fatal hypothermia, fatal hyperthermia and non-extreme temperature-related deaths. We analysed specific histological findings, focusing on samples from the liver, pancreas and kidney., Results: Between 1 January 2013 and 31 December 2016, 15 autopsies were performed for deaths related to extreme temperatures. They included 11 cases of fatal hypothermia (group A), four cases of fatal hyperthermia (group B) and eight controls (group C). Perinuclear hepatocyte vacuolisation was observed in seven cases of hypothermia, one case of hyperthermia and four controls. Pancreatic cytoarchitecture was well preserved in two cases of hypothermia, one case of hyperthermia and two controls. No particular microscopic feature was found in pancreatic samples. Renal epithelial tubular cell vacuolisation was observed in seven cases of hypothermia and one case of hyperthermia, while it was absent in all controls. Chromogranin A (CgA) was markedly positive in the pancreatic tissue of five cases of fatal hypothermia and one control, and mildly positive in one case of fatal hyperthermia. No significant p -values were observed for any comparisons ( p  > 0.05), except when hypothermia cases group were compared to the control group for the Armanni-Ebstein phenomenon test ( p  = 0.0078)., Conclusions: Although our study did not find a specific microscopic marker, hepatocyte vacuolisation, the Armanni-Ebstein phenomenon and pancreatic CgA positivity, taken together, may be useful tools to confirm hypo- and hyperthermia-related deaths, in addition to circumstantial and macroscopic findings.

Aim: Swarming motility is a virulence factor for Proteus mirabilis and is a coordinated multicellular movement of bacteria. In this study, we investigated the inhibitory effect of hyperthermia on bacterial swarming motility and antimicrobial resistance., Methods: Thirty-one P. mirabilis isolates were included in the study. Seven inoculated agar plates were incubated inside incubators with increasing temperature levels: at 36 °C (control) and 40-45 °C. On the next day, inhibition of swarming was evaluated and minimum paralyzing temperature (MPT) values were determined. An antimicrobial susceptibility test (antibiogram) is performed by exposing bacteria to increasing concentrations of antibiotics, in vitro . Thus, we used the Kirby-Bauer disk diffusion test as a screening method to analyze the antibiogram profiles of the isolates at 36 °C and 42 °C. Finally, a time-kill assay was performed to analyze the killing effect of hyperthermia (42 °C) on planktonic bacteria, in combination with the antibiotic meropenem at the first and third hours. A Wilcoxon signed-rank test was used to compare the killing effects of meropenem, hyperthermia and their combinations., Results: The median MPT value was determined as 44 °C. In the disk diffusion assay, susceptibility development was observed in 94% of isolates for at least one antibiotic. In the time-kill assay, we observed a significant killing effect of hyperthermia in combination with meropenem. Under the microscope, we observed the formation of spherical cells by the effect of heat., Conclusion: We conclude that these findings might be useful when employing the hyperthermia method to treat infectious diseases caused by P. mirabilis in the future.

Parked vehicles can create deadly environments for young children who are left unattended. This study was a descriptive analysis to describe circumstances leading to death in children left unattended in parked motor vehicles in India. Between 2011 and 2018, there were 16 incidents that resulted in 28 fatalities across India, mostly in the summer months. The majority of children (19/28) were aged 4-6 years, of whom 25 (89%) gained access to unattended vehicles and became accidentally locked in. Hyperthermia-related deaths are a poorly recognised type of vehicular injury in India; there has been no analysis to describe circumstances leading to such fatalities.

Background: Fever-range hyperthermia or fever-range temperature (hereafter FRT) improves survival and shortens disease duration in microbial infections. However, the mechanisms of these beneficial effects still remain elusive. We hypothesized that FRT might enhance cell responsiveness to infections by promoting cGAS-STING signaling to cause enhanced production of IFN-β. Objective: To investigate the effect fever-range hyperthermia on cGAS-STING pathway. Methods: RAW 264.7 and cGAS -/- RAW 264.7 cells, stimulated with 5μg/ml herring testis DNA (htDNA), were heated to 39.5°C and analyzed for the expression of cGAS, STING, IFN-β, and the synthesis of cGAMP and IRF3 phosphorylation. In vivo, wild type C57BL/6J mice were subjected to whole body hyperthermia (WBH) at 39.5°C. The mice were then challenged with influenza virus and analyzed for antiviral response in term of IFN-β expression, body weight and survival. Results: We found that 39.5°C FRT upregulated the expression of cGAS and STING, and induced the synthesis of cGAMP and production of IFN-β in htDNA-transfected RAW 264.7 cells more potently as compared to 37°C. Moreover, FRT+DMXAA-treated cells were better protected from vesicular stomatitis virus (VSV)-induced cytotoxicity in vitro in contrast to the nonprotected control (no FRT and DMXAA) or DMXAA treatment alone. In vivo, FRT at 39.5°C, co-administered with DMXAA, significantly induced the expression of IFN-β, showed reduced weight loss mice and exhibited 25% more survival over the course of 14 days as compared to DMXAA treated mice 37°C. Conclusion: We conclude that fever-range hyperthermia promotes cGAS-STING pathway to cause increased expression of IFN-β and mediate its antiviral effects.

Background: Thermal dose in clinical hyperthermia reported as cumulative equivalent minutes (CEM) at 43 °C (CEM43) and its variants are based on direct thermal cytotoxicity assuming Arrhenius 'break' at 43 °C. An alternative method centered on the actual time-temperature plot during each hyperthermia session and its prognostic feasibility is explored., Methods and Materials: Patients with bladder cancer treated with weekly deep hyperthermia followed by radiotherapy were evaluated. From intravesical temperature (T) recordings obtained every 10 secs, the area under the curve (AUC) was computed for each session for T  > 37 °C (AUC > 37 °C) and T  ≥ 39 °C (AUC ≥ 39 °C). These along with CEM43, CEM43(>37 °C), CEM43(≥39 °C), T mean , T min and T max were evaluated for bladder tumor control., Results: Seventy-four hyperthermia sessions were delivered in 18 patients (median: 4 sessions/patient). Two patients failed in the bladder. For both individual and summated hyperthermia sessions, the T mean , CEM43, CEM43(>37 °C), CEM43(≥39 °C), AUC > 37 °C and AUC ≥ 39 °C were significantly lower in patients who had a local relapse. Individual AUC ≥ 39 °C for patients with/without local bladder failure were 105.9 ± 58.3 °C-min and 177.9 ± 58.0 °C-min, respectively ( p  < 0.001), respectively. The median AUC ≥ 39 °C for each hyperthermia session in patients with bladder tumor control was 190 °C-min.p  < 0.001), respectively. The median AUC ≥ 39 °C for each hyperthermia session in patients with bladder tumor control was 190 °C-min., Conclusion: AUC ≥ 39 °C for each hyperthermia session represents the cumulative time-temperature distribution at clinically defined moderate hyperthermia in the range of 39 °C to 45 °C. It is a simple, mathematically computable parameter without any prior assumptions and appears to predict treatment outcome as evident from this study. However, its predictive ability as a thermal dose parameter merits further evaluation in a larger patient cohort.

Background: Cocaine (benzoylmethylecgonine) is one of the most widely used illegal psychostimulant drugs worldwide, and mortality from acute intoxication is increasing. Suppressing hyperthermia is effective in reducing cocaine-related mortality, but a definitive therapy has not yet been found. In this study, we assessed the ability of risperidone to attenuate acute cocaine-induced hyperthermia and delineated the mechanism of its action., Methods: Rats were injected i.p. with saline, risperidone, ketanserin, ritanserin, haloperidol, or SCH 23 390 before and after injection of cocaine (30 mg/kg) or with WAY-00 635, SB 206 553, or sulpiride before cocaine injection; thereafter, the rectal temperature was measured every 30 minutes for up to 4 hours. In vivo microdialysis was used to reveal the effect of risperidone on cocaine-induced elevation of dopamine (DA), serotonin (5-HT), and noradrenaline concentrations in the anterior hypothalamus. For post-administration experiments, saline or risperidone (0.5 mg/kg) were injected into rats, and cocaine (30 mg/kg) was injected 15 minutes later. For every 30 minutes thereafter, DA, 5-HT, and noradrenaline levels were measured for up to 240 minutes after cocaine administration., Results: Risperidone, 5-HT2A receptor antagonists, and D1 receptor antagonistic drugs prevented and reversed cocaine-induced hyperthermia. In contrast, receptor antagonists for 5-HT1A, 5-HT2B/2C, and D2 did not alter cocaine-induced hyperthermia. Risperidone treatment further attenuated cocaine-induced elevation of DA., Conclusions: Our results indicate that risperidone attenuates cocaine-induced hyperthermia primarily by blocking the activities of the 5-HT2A and D1 receptors and may be potentially useful for treating cocaine-induced acute hyperthermia in humans., (© The Author(s) 2020. Published by Oxford University Press on behalf of CINP.)

Background: Testicular hyperthermia can have negative effects on male fertility. Despite reported therapeutic benefits of curcumin, several factors often limit its application such as low water solubility and instable structure. Curcumin-loaded superparamagnetic iron oxide nanoparticles (SPIONs) were designed to solve its limitation of use. In the present study, we evaluated the effect of curcumin-loaded SPIONs on transient testicular hyperthermia in mouse., Materials and Method: A total of 18 adult male NMRI mice were divided into three groups (n = 6): I. Controls (Cont), II. Scrotal hyperthermia (Hyp), III. Scrotal hyperthermia + curcumin-loaded iron particles (240 μL) (Hyp + Cur). After seventy days, the animals were sacrificed and used for further molecular and stereological evaluations., Results: Sperm count, motility and viability significantly decreased in group hyp as compared to cont group. Furthermore, Sperm DNA fragmentation and cell apoptosis in testes increased remarkably in group hyp, compared with group cont. Stereological study showed a reduction in number of spermatogenic and Leydig cells, as well as reduced weight and volume of testes in hyp group. Degenerative appearance of testes exposed to hyperthermia was also observed. In addition, higher mRNA expression of inflammatory cytokines (IL1-α, IL6, and TNF-α) was detected in group hyp compared to cont group. However, curcumin-loaded SPIONs alleviated all of the pathologic changes in the Hyp + Cur group compared to the hyp group., Conclusion: Here, we used nanoparticle form of curcumin in testicular hyperthermia model and showed its ameliorating effects on testes damages caused by heat stress, which can be an appropriate method to overcome the problems that limit curcumin application in cases with increased intra testicular temperature., (Copyright © 2020. Published by Elsevier GmbH.)

In order to simulate the heat transfer in the process of hyperthermia, one-dimensional time-fractional Cattaneo heat transfer equation (TFHE) is established. Based on TFHE, the heat transfer model is solved by using finite difference method, because a single layer of biological tissue in vitro is irradiated by electromagnetic energy. The effect of power parameters (energy flux density P 0 , tissue attenuation coefficient h) and equation parameters (relaxation time τ q and fractional order β) on the prediction of temperature simulated by TFHE were studied. Furthermore, comparative studies on TFHE, Pennes and CV are performed and evaluated. In the heating process, because of the existence of relaxation time τ q , the temperature response of TFHE and CV are later than Pennes, leading to the lower temperature prediction of TFHE and CV than that of Pennes. The shorter the time is, the higher the energy is, and the more obvious the difference is., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Whole-body thermal and hydration clamps were used to evaluate their independent and combined impact on the electrical activity of the brain. It was hypothesised that those stresses would independently modify the electroencephalographic (EEG) responses, with those changes being greater when both stresses were superimposed., Methods: Alpha and beta spectral data (eyes closed) were collected from the frontal, central-parietal and occipital cortices of both hemispheres in resting, healthy and habitually active males (N = 8; mean age 25 years). Three dehydration states were investigated (euhydrated and 3% and 5% mass decrements) in each of two thermal states (normothermia [mean body temperature 36.3 °C] and moderate hyperthermia [38.4 °C]). The combination of those passively induced states yielded six levels of physiological strain, with the EEG data from each level separately examined using repeated-measures ANOVA with planned contrasts., Results: When averaged across the frontal cortices, alpha power was elevated relative to the occipital cortices during moderate hyperthermia (P = 0.049). Conversely, beta power was generally reduced during hyperthermia (P = 0.013). Neither the alpha nor beta power spectra responded to dehydration, nor did dehydration elevate the heat-induced responses (P > 0.05)., Conclusion: Moderate hyperthermia, but neither mild nor moderate dehydration, appeared to independently alter brain electrical activity. Moreover, the combination of moderate hyperthermia with 5% dehydration did not further increase those changes. That outcome was interpreted to mean that, when those states were superimposed, the resulting neurophysiological changes could almost exclusively be attributed to the thermal impact per se, rather than to their combined influences.

Purpose: This experiment was designed to quantify the independent and combined influences of hyperthermia and dehydration on effector control during rest and exercise., Methods: To achieve that, whole-body hydration of healthy adults (N = 8) was manipulated into each of three states (euhydrated, 3% and 5% dehydrated), and then clamped within each of two thermal states (normothermia [mean body temperature: 36.1 °C] and moderate hyperthermia [mean body temperature: 38.2 °C]). Those treatment combinations provided six levels of physiological strain, with resting physiological data collected at each level. The effects of isothermal, thermally unclamped and incremental exercise were then investigated in normothermic individuals during each level of hydration., Results: At rest, dehydration alone reduced urine flows by 83% (3% dehydrated) and 93% (5% dehydrated), while the reduction accompanying euhydrated hyperthermia was 86%. The sensitivities of renal water conservation to 3% dehydration (-21% mOsm -1  kg H 2 O -1 ) and moderate hyperthermia (-40% °C -1 ) were independent and powerful. Evidence was found for different renal mechanisms governing water conservation between those treatments. Cutaneous vasomotor and central cardiac responses were unresponsive to dehydration, but highly sensitive to passive thermal stress. Dehydration did not impair either whole-body or regional sweating during rest or exercise, and not even during incremental cycling to volitional exhaustion., Conclusion: In all instances, the physiological impact of these thermal- and hydration-state stresses was independently expressed, with no evidence of interactive influences. Renal water-conservation was independently and powerfully modified, exposing possible between-treatment differences in sodium reabsorption.

This study aimed to investigate ultrastructural synaptic alterations in rat hippocampus after in utero exposure to irradiation (IR) and postnatal exposure to hyperthermia (HT). There were four groups in each of the time points (3 rd and 6 th months). IR group: Pregnant rats were exposed to radiation on the 17 th gestational day. HT group: Hyperthermia was applied to the rat pups on the 10th day after their birth. IR+HT group: Both IR and HT were applied at the same time periods. Control group: No IR or HT was applied. Rat pups were sacrificed after 3 and 6 months. Thin sections from the dentate gyrus (DG) and the CA3 of hippocampus were evaluated for synapse numbers by electron microscopy. Synapses were counted, and statistical analysis was performed. Abnormalities in myelin sheath, mossy terminals and neuropil were observed in the CA3 and DG of all groups. The synapses in the CA3 region were significantly increased in the IR-3 rd month, IR-6 th month, and IR+HT-3 rd month groups vs control group. Synapses were significantly increased in the DG of HT-3 rd month group. A trend for an increase in synapse numbers was seen in the CA3 and DG. Increased number of synapses in the rat hippocampus may be due to mossy fiber sprouting, possibly caused by in utero irradiation and/or postnatal hyperthermia.

This article reviews the VA Manchester Healthcare System's journey to develop a robust simulation program and how an in situ simulation for malignant hyperthermia (MH) laid the foundation. Nurse educators collaborated with a certified registered nurse anesthetist to develop a simulation in the operating room using our MH protocol, which included the support of the Malignant Hyperthermia Association of the United States. The positive reaction from this in situ training led to additional simulation requests for the education department. [J Contin Educ Nurs. 2020;51(11):523-527.]., (Copyright 2020, SLACK Incorporated.)

Background and objectives: Exertional heat stroke (EHS) is a potentially lethal, hyperthermic condition that warrants immediate cooling to optimize the patient outcome. The study aimed to examine if a portable cooling vest meets the established cooling criteria (0.15 °C·min -1 or greater) for EHS treatment. It was hypothesized that a cooling vest will not meet the established cooling criteria for EHS treatment. Materials and Methods: Fourteen recreationally active participants (mean ± SD; male, n = 8; age, 25 ± 4 years; body mass, 86.7 ± 10.5 kg; body fat, 16.5 ± 5.2%; body surface area, 2.06 ± 0.15 m 2 . female, n = 6; 22 ± 2 years; 61.3 ± 6.7 kg; 22.8 ± 4.4%; 1.66 ± 0.11 m 2 ) exercised on a motorized treadmill in a hot climatic chamber (ambient temperature 39.8 ± 1.9 °C, relative humidity 37.4 ± 6.9%) until they reached rectal temperature (T RE ) >39 °C (mean T RE , 39.59 ± 0.38 °C). Following exercise, participants were cooled using either a cooling vest (VEST) or passive rest (PASS) in the climatic chamber until T RE reached 38.25 °C. Trials were assigned using randomized, counter-balanced crossover design. Results: There was a main effect of cooling modality type on cooling rates (F[1, 24] = 10.46, p < 0.01, η 2 p = 0.30), with a greater cooling rate observed in VEST (0.06 ± 0.02 °C·min -1 ) than PASS (0.04 ± 0.01 °C·min -1 ) (MD = 0.02, 95% CI = [0.01, 0.03]). There were also main effects of sex (F[1, 24] = 5.97, p = 0.02, η 2 p = 0.20) and cooling modality type (F[1, 24] = 4.38, p = 0.047, η 2 p = 0.15) on cooling duration, with a faster cooling time in female (26.9 min) than male participants (42.2 min) (MD = 15.3 min, 95% CI = [2.4, 28.2]) and faster cooling duration in VEST than PASS (MD = 13.1 min, 95% CI = [0.2, 26.0]). An increased body mass was associated with a decreased cooling rate in PASS (r = -0.580, p = 0.03); however, this association was not significant in vest (r = -0.252, p = 0.39). Conclusions: Although VEST exhibited a greater cooling capacity than PASS, VEST was far below an acceptable cooling rate for EHS treatment. VEST should not replace immediate whole-body cold-water immersion when EHS is suspected.

The spermatogenesis is temperature-dependent and heat stress have destructive effects on spermatogenesis and reduces sperm quality. Sixteen adult mice were allocated to two groups: hyperthermia and control groups. Scrotal hyperthermia was induced by water bath with 43°C for 30 min. Then, the spermatozoon was isolated through the tail region of epididymis for sperm parameters analysis. The testicular tissues were taken for stereological studies, hormonal assay, TUNEL assay and molecular studies. We found a marked decrease in sperm parameters and serum testosterone level in mice induced by scrotal hyperthermia as well as stereological analysis indicated a significant reduction in testicular cells and changes in the spatial arrangement of testicular cells in the scrotal hyperthermia groups compared to the control groups. Moreover, the TUNEL assay results showed that apoptotic cells were enhanced significantly in the group of scrotal hyperthermia compared to the control groups. Furthermore, scrotal hyperthermia caused a reduction in the expression of retinoic acid 8 (STRA8), c-kit and proliferating cell nuclear antigen (PCNA) genes in the scrotal hyperthermia groups compared to the control. According to results, induction of transient scrotal hyperthermia leads to a fluctuation in the spatial arrangement of testicular cells, which finally influences the normal function of spermatogenesis., (© 2020 Blackwell Verlag GmbH.)

Hyperthermia is caused by disturbance in the thermoregulatory system of the human body and requires emergency treatment to prevent disability or possible mortality. To design any therapeutic device for hyperthermia, an exhaustive effort is required to establish the extremities of such thermal traumas. In this context, the authors have incorporated the human-body exergy-balance equation to compute the hyperthermia thresholds. This is a pioneer attempt to model hyperthermia states. An induced-hyperthermia technique is used to evaluate the extremities of metabolic heat generation and other dependent parameters. Moreover, a case study is also presented to calculate the parameters of prime importance i.e. exergy consumption (EC) and entropy generation rate (δS g ) to provide the body's accumulative and exhaustive thermal energy maxima, respectively. Furthermore, the thresholds have been evaluated and simulated by the varying body and/or environmental conditions. The resulting states have been analysed to setup critical ranges to provide the guidelines for rehabilitation therapy. A thermal manikin has also been developed, mimicking the blood circulation in humans, to further substantiate the use of an exergy-based approach. The results indicate that the exergy-based approach is well suited to model hyperthermia at pathophysiological boundaries, contrary to existing approaches which predominantly are limited to the physiological domain., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Through this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm., Methods: Ten healthy subjects selected with strict screening criteria underwent testicular warming in a 43 °C water bath for 30 min a day for 10 consecutive days. Semen samples were collected 2 weeks before the first heat treatment and 6 weeks after the first heat treatment. Proteins from the samples were labeled with isobaric tags for relative and absolute quantitation and analyzed by two-dimensional liquid chromatography-tandem mass spectrometry., Results: In contrast to the control, of the 3446 proteins identified, 61 proteins were deregulated: 28 were up-regulated and 33 were down-regulated. Approximately 95% of the differentially expressed proteins were found to participate in spermatogenesis, fertilization, or other aspects of reproduction. In particular, the expression of sperm motility and energy metabolism-related proteins AKAP4, SPESP1, ODF1, ODF2, GAPDHS, and ACTRT2, validated by western blotting of the proteins obtained from human and mouse samples, tended to be reduced under scrotal hyperthermia., Conclusions: The results indicated that the proteins AKAP4, ODF1, ODF2, GAPDHS, SPESP1, and ACTRT2, play an important role in the heat-induced reversible reduction in sperm concentration and motility and have the potential to be the biomarkers and clinical targets for scrotal heat treatment induced male infertility.

Background: Hyperthermia is relatively rare during general anesthesia; however, a few studies have been conducted on hyperthermia and the neuromuscular blockade (NMB) induced by rocuronium, and the reversal of NMB by sugammadex. We investigated the effect of hyperthermia status on the NMB induced by rocuronium, and its reversal by sugammadex, in isolated phrenic nerve hemidiaphragm (PNHD) preparations of the rat., Methods: Thirty-three male Sprague-Dawley rat PNHD preparations were randomly assigned to three groups at different temperatures (36 °C, 38 °C, and 40 °C; each group, n = 11, in Krebs solution). The train-of-four (TOF) and twitch height responses were checked mechanomyographically. The PNHD were treated with progressively increasing doses of rocuronium and three effective concentrations (ECs), EC50, EC90, and EC95, of rocuronium were analyzed in each group via nonlinear regression analysis. Then, sugammadex was administered in doses equimolar to rocuronium. Thereafter, the T1 height (%), TOFR (%) and the duration index were measured., Results: The EC of rocuronium (EC50, EC90, and EC95) decreased significantly in accordance with increasing temperature. The groups at 36 °C and 40 °C showed clear differences in all areas (all P < 0.001). Moreover, the T1 height (%) and the duration index upon sugammadex administration showed faster recovery results in the36 °C than the 38 °C and 40 °C groups., Conclusion: A rise of temperature from 38 °C to 40 °C in rat PNHD preparations proportionally enhanced the NMB induced by rocuronium. In addition, equimolar doses of sugammadex to the administered rocuronium showed a slower recovery time as the temperature rises.

Severe hyperthermia from classical or exertional heatstroke, or from drug ingestion or other noninfective pyrogens, is associated with a high mortality and morbidity. A systemic pro-inflammatory response occurs during heatstroke, characterized by elevated cytokines with endotoxemia from elevated lipopolysaccharide (LPS) levels. Corticosteroids reduce LPS and cytokine levels, suggesting that they may improve outcome. A systematic review searching Embase, MEDLINE, and PubMed from the earliest date available until September 2019 was conducted, according to the PRISMA guidelines, with five papers identified. In four studies, systemic steroids administered before or at the onset of heat stress improved mortality or reduced organ dysfunction. Survival time was greatest when steroid administration preceded heat stress. In one study, a nonsignificant increase in mortality was seen. A dose response was observed, with higher doses extending survival time. Animal studies suggest that steroids improve mortality and/or organ dysfunction after an episode of heat stress or extreme hyperthermia., (© 2020 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics.)