Body temperature (BT) is an important indicator used during physical examination to assess the animal's health and disturbances to its body’s homeostasis. Digital rectal thermometry (DRT) is the current gold standard measurement method in small animals’ clinical veterinary medicine, surrogating for core body temperature. However, this method has multiple disadvantages, including inaccuracy due to local rectal variations, poor clinicians' safety, animals' discomfort, stress response, and relatively long measuring time. Auricular (tympanic membrane) infrared thermometry (AIRT) could be an attractive alternative, as it represents the hypothalamic temperature well. However, studies assessing its accuracy are scarce and absent in veterinary medicine. This study simultaneously assessed the BT of 100 hospitalized dogs and cats using DRT and AIRT to evaluate the agreement between them, analyzing their accuracy using the coefficient of variation. While DRT was more accurate than AIRT, both methods were reliable, well correlated (R 2 = 0.694), and in good agreement. Measurements by AIRT were mostly lower than by DRT, justifying using a correction factor of 0.5°C, which improved the agreement and correlation between the methods (R 2 = 0.833). Our findings suggest that AIRT was reliable and could substitute DRT when using the latter is impossible or inadvisable.

Septic peritonitis (SP) is a life-threating condition. Determining prognosis for dogs suffering from SP remains challenging. Extracellular histones exert cytotoxic, prothrombotic and proinflammatory effects. Our objective was to investigate serum general histone concentrations (sHs) as biomarkers of disease severity and outcome in dogs with naturally occurring SP. Blood samples were collected upon admission and 24 hours post admission from 21 dogs with SP and from 7 healthy controls. Serum general histone concentrations (median; IQR) upon admission were higher in dogs with SP compared to controls (34.2 ng/ml; 39.1 ng/ml vs. 7.3 ng/ml; 1.7 ng/ml; P=0.001) and sHs significantly decreased 24 hours post admission in dogs with SP (34.4 ng/ml; 39.3 ng/ml vs. 24.2 ng/ml; 11 ng/ml; P=0.018). Serum histones were higher among survivors compared to non-survivors (45.5 ng/ml; 37 ng/ml vs. 24.0 ng/ml; 12 ng/ml; P=0.03). This data demonstrates that sHs concentrations significantly increase in dogs with SP and decrease after hospitalization. Future studies are warranted to investigate the reverse relationship between outcome and sHs.

Thermal intolerance may limit activity in hostile environments. After heat illness, two physiologically distinct phenotypes evolve: heat tolerant (HT) and heat intolerant (HI). The recognition that heat illness alters gene expression justified revisiting the established physiological concept of HI. We used a DNA microarray to examine the global transcriptional response in peripheral blood mononuclear cells (PMBCs) from HI and HT phenotypes, categorized 2-mo postheat injury using a functional physiological heat-tolerance test (HTT, 40°C)-Recovery (R, 24°C) protocol. The impact of recurrent heat stress was studied in vitro using peripheral blood mononuclear cells (PBMCs) from controls (participants with no history of heat injury), HI, and HT (categorized by functional HTT) with a customized NanoString array. There were significant differences under basal conditions between the HI and HT. HI were more immunological alerted. Almost no shared genes were found between end-HTT and recovery phases, suggesting vast cellular plasticity. In HI, mitochondrial function was dysregulated, canonical pathways associated with exercise endurance-NRF2 and insulin were downregulated, whereas AMPK and peroxisome proliferator-activated receptor (PPAR) were upregulated. HT exhibited reciprocal responses, suggesting that energy dysregulation found in HI interfered with performance in the heat. The endoplasmic-reticulum stress response was also suppressed in HI. In vitro HTT (43°C) abolished differences between HI and HT PBMCs including the HSPs genes, whereas controls showed profound HSPs upregulation.

1) The first evidence of the beneficial impact of Long-Term-Heat-Acclimation (LTHA) on cardio-vascular compliance was the positive inotropic response and improved left ventricular (LV) compliance noted when isolated hearts from LTHA rats were studied. Human echo study demonstrates that passive HA affects the right ventricle and the atria as well. 2) There is a cross-talk between vascular and cardiac compliance. Vascular compliance per se is defined by central venous pressure—Blood volume relationship—Global Vascular Compliance (GVC). It is determined by the sum of the vascular compliance of the vessels in every organ in any physiological state, varies with LTHA and thus influences cardiac performance. LTHA improves endothelial function, increases NO (nitric oxide) production, in-turn stimulating alterations in ECM (extracellular matrix) via the TGF β1-SMAD pathway. 3) LTHA is associated with transformation from fast to slow myosin, heat acclimation ischemic/hypoxic cross-tolerance and alterations in the extracellular matrix. 4) A human translational study demonstrated improved LV compliance following bypass surgery in LTHA subjects compared to controls. 5) Diastolic dysfunction and the impact of comorbidities with vascular and non- vascular origins are major contributors to the syndrome of heart failure with preserved ejection function (HFPEF). Unfortunately, there is a paucity of treatment modalities that improve diastolic dysfunction. 6) In the current mini-review we suggest that LTHA may be beneficial to HFPEF patients by remodeling cardiac compliance and vascular response.

New Findings What is the topic of this review? This review outlines the history of research on epigenetic adaptations to heat exposure. The perspective taken is that adaptations reflect properties of hormesis, whereby low, repeated doses of heat induce adaptation (acclimation/acclimatization); whereas brief, life‐threatening exposures can induce maladaptive responses. What advances does it highlight? The epigenetic mechanisms underlying acclimation/acclimatization comprise specific molecular programmes on histones that regulate heat shock proteins transcriptionally and protect the organism from subsequent heat exposures, even after long delays. The epigenetic signalling underlying maladaptive responses might rely, in part, on extensive changes in DNA methylation that are sustained over time and might contribute to later health challenges. AbstractEpigenetics plays a strong role in molecular adaptations to heat by producing a molecular memory of past environmental exposures. Moderate heat, over long periods of time, induces an ‘adaptive’ epigenetic memory, resulting in a condition of ‘resilience’ to future heat exposures or cross‐tolerance to other forms of toxic stress. In contrast, intense, life‐threatening heat exposures, such as severe heat stroke, can result in a ‘maladaptive’ epigenetic memory that can place an organism at risk of later health complications. These cellular memories are coded by post‐translational modifications of histones on the nucleosomes and/or by changes in DNA methylation. They operate by inducing changes in the level of gene transcription and therefore phenotype. The adaptive response to heat acclimation functions, in part, by facilitating transcription of essential heat shock proteins and exhibits a biphasic short programme (maintaining DNA integrity, followed by a long‐term consolidation). The latter accelerates acclimation responses after de‐acclimation. Although less studied, the maladaptive responses to heat stroke appear to be coded in long‐lasting changes in DNA methylation near the promoter region of genes involved with basic cell function. Whether these memories are also encoded in histone modifications is not yet known. There is considerable evidence that both adaptive and maladaptive epigenetic responses to heat can be inherited, although most evidence comes from lower organisms. Future challenges include understanding the signalling mechanisms responsible and discovering new ways to promote adaptive responses while suppressing maladaptive responses to heat, as all life forms adapt to life on a warming planet.

Introduction: Sailors assigned to Warships endure heavy operational workloads, shift work, and austere, challenging sleeping environments. Decision-support tools that provide real-time monitoring and management of crew endurance can provide critical support in identifying and mitigating these threats. Existing attempts to address these issues are limited, relying on self-assessment, and placing the reporting burden on Sailors. The goal of this research program is to test the feasibility of a monitoring capability that blends Sailor biometric data with contextual indicators to create a summary of fatigue and crew endurance status. Methods: This study is ongoing, with two completed underway data collections on United States Navy warships (n = 535). Volunteers are active-duty Sailors/Marines who wear two devices (the Fatigue Science Readiband and Oura Ring) and answer questions daily that capture contextual health and behavioral data. Using Smartabase (a data aggregation and visualization/dashboard platform), self-report data are combined with wearable biometric data [e.g., heart rate (HR) and HR variability, skin temperature deviation, body movement, sleep]. Results: Identifying problematic cases requires detecting anomalous cases. Within a dashboard, trend data may be particularly useful. For example, Fig. 1 illustrates what a Commanding Officer could see in a dashboard for daily crew sleep at the department level. On average, participants slept 6 hrs/day (less than the 7 hours required per Navy guidelines), but Sailors in engineering routinely obtained closer to 5 hrs/day. At the individual level, threshold-based alerts can prompt action towards a specific Sailor. For example, one Sailor flagged on multiple physiological health indicators (deviation from previous days, as measured by z-scores: temperature deviation > 5, respiration > 4, lowest HR > 2). This individual also self-reported cough, headache, and brain fog symptoms. On previous days, this Sailor had reported “poor” sleep and multiple sleep disturbances. Discussion/conclusions: Though this research is ongoing, several insights are emerging. Group level data may be important for visualizing overall trends while individual level data may be used to draw attention to specific problematic cases that warrant direct follow-up. To establish useful criteria for the flag alert system, contextual data must be used to help interpret wearable data and to develop a deeper understanding of individual phenotypic profiles. Finally, dashboard value ultimately depends on making wearable information actionable, and that can only come from direct engagement and buy-in from leadership and crew. Disclaimer: I am an employee of the U.S. Government. This work was prepared as part of my official duties. Title 17, U.S.C., §105 provides that copyright protection under this title is not available for any work of the U.S. Government. Title 17, U.S.C., §101 defines a U.S. Government work as a work prepared by a military Service member or employee of the U.S. Government as part of that person’s official duties. This work was supported by JPC-5 under work unit no. N2017. The views expressed in this abstract reflect the results of research conducted by the author(s) and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. The study protocol was approved by the Naval Health Research Center Institutional Review Board in compliance with all applicable Federal regulations governing the protection of human subjects. Research data were derived from an approved Naval Health Research Center Institutional Review Board protocol number NHRC.2021.0003.

Exposure to high ambient temperature is a stressor that influences both biological and behavioral functions and has been previously shown to have an extensive impact on brain structure and function. Physiological, cellular and behavioral responses to heat-stress (HS) (40–41 °C, 2 h) were evaluated in adult male Sprague-Dawley rats. The effect of HS exposure before predator-scent stress (PSS) exposure (i.e., HS preconditioning) was examined. Finally, a possible mechanism of HS-preconditioning to PSS was investigated. Immunohistochemical analyses of chosen cellular markers were performed in the hippocampus and in the hypothalamic paraventricular nucleus (PVN). Plasma corticosterone levels were evaluated, and the behavioral assessment included the elevated plus-maze (EPM) and the acoustic startle response (ASR) paradigms. Endogenous levels of heat shock protein (HSP)-70 were manipulated using an amino acid (L-glutamine) and a pharmacological agent (Doxazosin). A single exposure to an acute HS resulted in decreased body mass (BM), increased body temperature and increased corticosterone levels. Additionally, extensive cellular, but not behavioral changes were noted. HS-preconditioning provided behavioral resiliency to anxiety-like behavior associated with PSS, possibly through the induction of HSP-70. Targeting of HSP-70 is an attractive strategy for stress-related psychopathology treatment.

Abstract The effect of 30 days of β-alanine supplementation on neurophysiological responses of animals exposed to an acute heat stress (HS) was examined. Animals were randomized to one of three groups; exposed to HS (120 min at 40–41 °C) and fed a normal diet (EXP; n = 12); EXP and supplemented with β-alanine (EXP + BA; n = 10); or not exposed (CTL; n = 10). Hippocampal (CA1, CA3 and DG) and hypothalamic (PVN) immunoreactive (ir) cell numbers of COX2, IBA-1, BDNF, NPY and HSP70 were analyzed. Three animals in EXP and one in EXP–BA did not survive the HS, however no significant difference (p = 0.146) was noted in survival rate in EXP + BA. The % change in rectal temperature was significantly lower (p = 0.04) in EXP + BA than EXP. Elevations (p’s < 0.05) in COX-2, IBA-1 and HSP70 ir-cell numbers were noted in animals exposed to HS in all subregions. COX-2 ir-cell numbers were attenuated for EXP + BA in CA1 (p = 0.02) and PVN (p = 0.015) compared to EXP. No difference in COX-2 ir-cell numbers was noted between CTL and EXP + BA at CA1. BDNF-ir cell numbers in CA1, DG and PVN were reduced (p’s < 0.05) during HS compared to CTL. No difference in BDNF-ir cell numbers was noted between EXP + BA and CTL in CA3 and PVN. NPY-ir density was reduced in exposed animals in all subregions, but NPY-ir density for EXP-BA was greater than EXP in CA3 (p < 0.001) and PVN (p = 0.04). β-Alanine supplementation attenuated the thermoregulatory and inflammatory responses and maintained neurotrophin and neuropeptide levels during acute HS. Further research is necessary to determine whether β-alanine supplementation can increase survival rate during a heat stress.

The epigenetic memory of a cell or an organ is recognized when instructions like 'transcribe' or 'do not transcribe' a gene, associated with chromatin remodelling, maintaining the chromatin-DNA package in a silent or active state, are given. In other words, transcription is altered without any changes to the inherited DNA sequence. These modifications to gene expression influence cell properties and behaviour, determining resilience or vulnerability to recurring events (Cramer et al. 2019). Environmental stress may play a vital role in epigenetic memory. Unfortunately, our knowledge of the impact of environmental heat stress on epigenetic memory is sparse. The publication by Pandolf et al. (1977), reporting that repeated acclimatization following 18 days of acclimatization-decay was profoundly faster than the period required to achieve initial acclimatization, suggesting that acclimatization (and acclimation) has a memory, drew our attention to the possibility that heat stress has epigenetic impacts. Using our established animal model of acclimation-memory we employed the heat shock proteins (HSPs) system as a prototype to determine whether heat-acclimation-memory involves epigenetics. More specifically, we studied histone modifications at the heat shock element (HSE) binding site of the promoters of hsp70 and hsp90 in rat hearts. Our findings that HSPs, Hsf1 and chromatin remodellers are in the gene clusters with altered expression throughout heat acclimation (AC), de-acclimation (DeAC) and re-acclimation (ReAC), in tandem with the physiological loss of the heat acclimated phenotype upon DeAC and its reacquisition following ReAC, provided the rational for our hypothesis that AC memory is linked to chromatin remodelling and epigenetic machinery. AC mediated cardio-protection via cross-tolerance mechanisms, an inseparable feature of heat acclimation, based on shared alerted genes, served as a marker of acclimation (Tetievsky & Horowitz, 2010). We demonstrated that constitutively acetylated histone H4 and the preserved euchromatin state throughout AC-DeAC-ReAC lead to rapid acclimatory memory (2 days upon ReAC (vs. 30 days to achieve initial AC phenotype) due to prompt HSF-1-HSE binding and subsequent activation of the cytoprotective heat shock response (HSR). The DeAC phase demonstrated a continuum of changes in a variety of genes linked to the ambient temperature (Tetievsky & Horowitz, 2010; Tetievsky et al. 2014). Schermann et al. (2018) predicted that heat injured subjects are more susceptible to recurrent heat injury. This prediction highlighted the link between epigenetics and heat stress, suggesting that the balance between resilience and vulnerability was disrupted. Before the report in this issue of The Journal of Physiology by Murray et al. (2021), the only evidence on the epigenetic-heat stress relationship in adults was our work on heat acclimation memory (Tetievsky & Horowitz, 2010; Tetievsky et al. 2014) and the Schnermann et al. study. The investigation by Murray et al. (2021) is the first study using an animal EHS (exertional heat stroke) model, investigating whether epigenetic mechanisms are involved with consistent changes produced by exertional heat stroke. Numerous studies on the role of epigenetics in innate or adaptive memory focus on the immune system. EHS is characterized by immunosuppression, increased susceptibility to viral infection and altered HSR. Accordingly, Murray et al. (2021) investigated whether EHS produces a lasting epigenetic memory in monocytes and whether there are phenotypic alterations consistent with these changes. Initially monocytes, isolated from bone marrow of female mice were analysed for methylation 4 and 30 days after EHS. Many changes were found in the DNA methylome at both time points, including alterations in the promoter regions of genes involved with immune responsiveness. The authors then challenged whole blood at 30 days with lipopolysaccharide (LPS) to measure cytokine secretion. The increase in proinflammatory cytokine IL-6 and inflammatory cytokine TNFα were attenuated in the EHS vs. controls. There were also differential changes in HSP genes: HSP70 decreased and HSP90 was upregulated in response to an in-vitro heat challenge. Collectively, the data presented by Murray et al. (2021) support the hypothesis that EHS induced long-term molecular changes that may be associated with an altered epigenetic profile. In addition to the methylome changes in bone marrow cells per se, these cells interact with other systems, including brain areas that affect behavioural or physiological responses, e.g. the hypophysis-adrenal axis (e.g. Cramer et al. 2019), thereby increasing corticosteroid levels, and also the immune system leading to the attenuation of the anti-inflammatory TNFα. Although Murray et al. (2021) reported elevated corticosteroids for 3–4 days post EHS "possibly sufficient to reprogram the immune cells for extended period", Cramer et al. (2019), using a model of chicks before establishment of their thermoregulatory system, showed unequivocally that 24 h of exposure to high levels of corticosteroids is sufficient to induce an epigenetic disruption of resilience to severe heat stress and decrease HSP 70kD, the consensus stress protein. The importance of Murray et al.'s investigation stems from the solid evidence that EHS induces long-term epigenetic memory, suppressing the immune system for almost a month, supporting the prediction that heat intolerant subjects are more susceptible to recurrent EHS (Schermann et al. 2018). The rate of decay, or whether there is any decay of the effects of the stressful event, and which systems are affected remain unknown. Taken together, it seems that heat stress affects the epigenetic machinery in a dose dependent manner, where exposure to moderate stress promotes the development of the adapted, resilient phenotype (Tetievsky & Horowitz, 2010; Tetievsky et al. 2014; Cramer et al. 2019), whereas severe stress causes long-lasting damage (Schermann et al. 2018; Murray et al. 2021). None. Sole author. None.

Blood-contaminated fingermarks (FMs) found in violent crime scenes may directly connect the suspect to the crime by linking the FM to the suspect and the DNA from the blood to the victim. However, marks that are incomparable are considered "dead-evidence" as the link to the suspect is lost. In this study, a novel approach was attempted to uncover the trace amount of touch DNA of the suspect in such marks. We examined the effect of two enhancement methods, ninhydrin (NIN) and amido black (AB), on DNA recovery from blood-contaminated FMs. A total of 108 fingerprints were deposited in three sets of depleted blood prints, blood-contaminated FMs, and latent FMs. All FMs were developed by either NIN or AB, or left undeveloped as reference followed by the quantification of the total DNA amount. This work shows that while AB had a detrimental effect on the quantity of blood-derived DNA specifically, reducing it by half, no similar effect was observed for touch DNA in latent FMs. This reduction led to the alteration of the major-to-minor DNA profile ratio to 70:30, thus enabling to obtain two distinct DNA profiles of the suspect from the touch DNA as well as the victim's profile from the blood. From an operational perspective, the use of AB in crime scenes may have an added value to retrieve the crucial DNA profile of the suspect, thus resurrecting a "dead-evidence."

Heat acclimation (HA) induces metabolic plasticity to resist the effects of environmental heat with cross-tolerance to novel stressors such as oxygen supply perturbations, exercise, and alike. Our previous results indicated that hypoxia inducible transcription factor (HIF-1α) contributes to this adaptive process. In the present study, we link functional studies in isolated cardiomyocytes, with molecular and biochemical studies of cardiac mitochondria and demonstrate that HA remodels mitochondrial metabolism and performance. We observed the significant role that HIF-1α plays in the HA heart, as HA reduces oxidative stress during ischemia by shifting mitochondrial substrate preference towards pyruvate, with elevated level and activity of mitochondrial LDH (LDHb), acting a pivotal role. Increased antioxidative capacity to encounter hazards is implicated. These results deepen our understanding of heat acclimation-mediated cross tolerance (HACT), in which adaptive bioenergetic-mechanisms counteract the hazards of oxidative stress.

Due to an unfortunate misunderstanding, the top part of Figures 2 and 3 are not correctly displayed. The original article has been corrected and the proper version of Figures 2 and 3 is also published here.

Traumatic brain injury (TBI), caused by mechanical impact to the brain, is a leading cause of death and disability among young adults, with slow and often incomplete recovery. Preemptive treatment strategies may increase the injury resilience of high-risk populations such as soldiers and athletes. In this work, the xanthophyll carotenoid Astaxanthin was examined as a potential nutritional preconditioning method in mice (sabra strain) to increase their resilience prior to TBI in a closed head injury (CHI) model. The effect of Astaxanthin pretreatment on heat shock protein (HSP) dynamics and functional outcome after CHI was explored by gavage or free eating (in pellet form) for 2 weeks before CHI. Assessment of neuromotor function by the neurological severity score (NSS) revealed significant improvement in the Astaxanthin gavage-treated group (100 mg/kg, ATX) during recovery compared to the gavage-treated olive oil group (OIL), beginning at 24 h post-CHI and lasting throughout 28 days (p < 0.007). Astaxanthin pretreatment in pellet form produced a smaller improvement in NSS vs. posttreatment at 7 days post-CHI (p < 0.05). Cognitive and behavioral evaluation using the novel object recognition test (ORT) and the Y Maze test revealed an advantage for Astaxanthin administration via free eating vs. standard chow during recovery post-CHI (ORT at 3 days, p < 0.035; improvement in Y Maze score from 2 to 29 days, p < 0.02). HSP profile and anxiety (open field test) were not significantly affected by Astaxanthin. In conclusion, astaxanthin pretreatment may contribute to improved recovery post-TBI in mice and is influenced by the form of administration.

The effect of 30-days of β-alanine (BA) supplementation on heat shock protein 70 (HSP70), inflammatory and neurotrophin responses in the hippocampus and hypothalamus of rats exposed to an acute heat stress was investigated. Animals were randomized to either a control (CTL) group or BA supplementation (100mg·kg−1) group. All animal were fed a normal diet and only differed regarding supplementation. Following supplementation animals were either exposed to the heat stress (120 min at 40–41°C) or were unexposed. Following the acute heat stress, or at the end of the supplementation period, animals were harvested and their brains removed. Immunohistochemical technique was used to detect expression of HSP70, brain-derived neurotrophic factor (BDNF), cyclooxygenase-2 (COX2) and neuropeptide Y (NPY) in the hippocampus subregions and paraventricular nuclear (PVN) region of the hypothalamus. Three animals in CTL and one in BA did not survive the heat stress. Significant attenuation (P's < 0.005) in BDNF expression was noted in animals exposed to the heat stress compared to unexposed in all subregions (CA1, CA3 and DG) of the hippocampus and PVN. A significant elevation in BDNF expression in the CA3 subregion of rats fed BA and exposed to the heat stress was observed compared to exposed CTL animals. Significant elevations in COX2 was also noted in the CA1 and CA3 subregions in exposed compared to unexposed animals. COX2 expression was significantly greater (P ≤ 0.0065) in CTL compared with BA during heat exposure in the CA1 subregion of the hippocampus. Animals supplemented with BA also realized significantly higher HSP70 expression (P = 0.02) in the CA3 subregion of the hippocampus compared to CTL. Significant differences (P's < 0.05) in NPY expression in all subregions of the hippocampus and PVN were noted between exposed and unexposed animals. However, NPY expression was significantly higher (P ≤ 0.03) for BA compared to CTL in exposed animals in the PVN. Results suggested that BA supplementation appeared to increase resiliency to an acute heat stress and reduced the inflammatory response, while increasing HSP70 and neurotrophins expression. Natural Alternatives International Inc., Carlsbad, CA, USA.

Heatstroke (HS) is an acute, progressive life-threatening emergency. Animals, including military working dogs (IDFMWD), rapidly activate cytoprotective processes, e.g., heat shock proteins (HSPs) and antioxidative molecules, in response to heat stress. We hypothesized that serum HSPs (eHSP72) and oxidative stress markers would differ in IDFMWD with a history of HS compared with controls and thus could be used to detect susceptibility to recurrent HS. eHSPs concentration, oxidative stress markers, and systemic physiological parameters were studied in dogs with and without histories of HS, undergoing indoor or outdoor training. Treadmill physical performance tests (PPTs) were conducted indoors at 22 °C (groups C-I and HS-I) or outdoors under heat stress conditions of 36 °C; 60% humidity (groups C-O and HS-O). Pre-, immediately post-, and 45 min post-PPT heart rate (HR), respiratory rate, and rectal temperature (Tre) were recorded in all dogs. Likewise, blood samples were collected and eHSP72, venous blood gas analysis, and lactate and creatine kinase activity (CK) were assayed. Serum uric acid (sUA) and total serum redox potential (TRP) were measured only in the indoor group. Immediately post-PPT under both environmental conditions, Tre, HR, eHSP, sUA, and TRP (only measured in indoor PPT) significantly (P < 0.05) increased, whereas venous blood pH and bicarbonate decreased significantly (P < 0.05). Between groups comparisons demonstrated significant differences in basal HR and post-PPT Tre immediately after outdoor PPT. eHSP72 induction, CK, sUA, and serum TRP remained significantly higher in the HS group during post-PPT recovery. Taken together, animals with a history of HS have different results, and this signature of previous HS may predict altered heat sensitivity.

Objectives: To examine the supplementation effects of the xanthophyll carotenoid Astaxanthin on physical performance and exertional heat strain in humans. Design: A randomized double blind placebo controlled trial. Methods: Twenty two male participants (Age: 23.14 ± 3.5 y, height: 175 ± 6 cm, body mass: 69.6 ± 8.7 kg, % body fat: 16.8 ± 3.8) received placebo (PLA, n = 10) or Astaxanthin (ATX, n = 12) 12 mg/day Per os (P.O), for 30 days, and were tested pre and post-supplementation with a maximal oxygen uptake (VO2 Max) test and the heat tolerance test (HTT) (2 h walk at 40°C, 40% relative humidity (RH), 5 kph, 2% incline). NIH database registration no. NCT02088242. Gas exchange, Heart rate (HR), Relative perceived exertion (RPE), and blood lactate were measured during the VO2 Max test. Heart rate (HR), rectal (Trec), and skin (Tskin) temperatures, RPE, and sweat rate (SR) were monitored in the HTT. Serum heat shock protein 72 (HSP72), Creatine phospho-kinase (CPK), C-reactive protein (CRP), and lipid profile were measured before and after the test. Results: The rise in blood lactate caused by the VO2 Max test was significantly diminished in the ATX group (9.4 ± 3.1 and 13.0 ± 3.1 mmole*l-1 in the ATX and PLA groups, respectively P < 0.02), as was the change in oxygen uptake during recovery (-2.02 ± 0.64 and 0.83 ± 0.79% of VO2 Max in the ATX and PLA group, respectively, p = 0.001). No significant differences were observed in the anaerobic threshold or VO2 Max. In the HTT, no significant physiological or biochemical differences were observed (HR <120 bpm, Trec rose by ~1°C to <38°C, no difference in SR). Conclusions: Astaxanthin supplementation improved exercise recovery. No benefit was observed for ATX over PLA in response to heat stress. Further examination of Astaxanthin in higher exertional heat strain is required.

Impact related traumatic brain injury (TBI) commonly influences high‐risk populations such as contact sports athletes and combat soldiers. Recovery results in mild to severe loss of motor and cognitive function. Prophylactic protection to enhance resilience and improve the rate and extent of recovery by nutrient supplementation is currently limited. Astaxanthin is a natural xantophyll carotenoid supplement which readily crosses the blood brain barrier (BBB) and was previously shown to improve recovery in a brain ischemia‐reperfusion model when administered post injury.The study objective was to examine the effects of Astaxanthin pre‐supplementation on the motor and cognitive aspects of recovery from a closed head injury (CHI) model in mice.Methodsmale sabra mice were treated with Astaxanthin 100 mg/Kg per day in olive oil by gavage (XO), or olive oil (O) or in pellet form as 1% Astaxanthin in animal food by free eating (X) for 2 weeks, exposed to a CHI model, and followed over a one month recovery period. Motor skills were assessed using the neurological severity score (NSS) at 1, 24, 48, and 72 hours and weekly post injury. Cognitive skills were assessed using the Open filed, and Y‐Maze tests on days 2 and 29 post injury, and the novel object recognition (ORT) test on days 3 and 30 post injury.Ethics: all animal experiments were approved by the Hebrew University authority for biological and biomedical models ethical review board (registration numbers: MD‐13‐13734‐4 & MD‐16‐14842‐4).ResultsNSS scores revealed a significant improvement in motor skills recovery (ΔNSS=1.25±0.16 vs. 0.5±0.27 in XO vs. O, respectively, p=0.001), which began on week 2 and lasted to 4 w. Additional cognitive improvement was demonstrated in the Y‐maze on Day 29: 44.57±3.22% vs. 36.46±1.95% of exploration time spent in the novel arm for XO vs. O, respectively, p=0.03). The results of the open field and ORT tests did not significantly differ between groups.When Astaxanthin supplementation was administered in pellet form (X), a considerably smaller influence was observed in the NSS compared to XO, while cognition (open field, Y‐Maze, ORT) remained unaffected. Post injury X supplementation with or without pre supplementation did not improve results.ConclusionResults suggest an advantage to XO over X and O in motor and cognitive skills recovery. The results of the effect of XO on NSS and on cognitive function, versus the lack of similar motor and cognitive effects with X, suggest a contribution of the combined XO administration to motor and cognitive parameters and warrants further work to elucidate its mechanism as well as the effects of post injury XO supplementation.Support or Funding InformationThis work was funded by the IDF medical corps research authorityThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

During the period of 1986–1997 the first 4 publications on the mechanical and metabolic properties of heat acclimated rat's heart were published. The outcome of these studies implied that heat acclimation, sedentary as well as combined with exercise training, confers long lasting protection against ischemic/reperfusion insult. These results promoted a clinical study on patients with coronary artery disease scheduled for elective coronary artery bypass operations aiming to elucidate whether exploitation of environmental stress can be translated into human benefits by improving physiological recovery. During the 1998 study, immediate-post operative chamber stiffness was assessed in patients acclimatized to heat and low intensity training in the desert (spring in the Dead Sea, 17–33°C) vs. patients in colder weather (spring in non-desert areas, 6–19°C) via echocardiogram acquisition simultaneous with left atrial pressure measurement during fast intravascular fluid bolus administration. We showed that patients undergoing “heat acclimatization combined with exercise training” were less susceptible to ischemic injury, therefore expressing less diastolic dysfunction after cardiopulmonary bypass compared to non-acclimatized patients. This was the first clinical translational study on cardiac patients, while exploiting environmental harsh conditions for human benefits. The original experimental data are described and discussed in view of the past as well as the present knowledge of the protective mechanisms induced by Heat Acclimation Mediated Cross-tolerance.

Introduction: Heat stress is a major concern in active populations such as athletes and soldiers. To date, no substance is known to enhance heat tolerance via a preconditioning strategy. Astaxanthin is a widely used xanthophyll carotenoid food supplement extensively studied for its health benefits. Early positive results in a rodent passive heat stress model led us to examine its effects as a preconditioning agent to heat stress in humans. The purpose of this study was to evaluate the influence of Astaxanthin supplementation on exertional heat stress and aerobic performance in humans.

The deep old mine in South Africa, in the early 19th century, was a unique environmental occupational setting. The pioneering heat-acclimation procedures used to prevent fatalities and increase yield provide a template to dissect the evolution of ideas and physiology underling human heat acclimation, especially when the physiologicgenomic linkage is examined concomitantly. The first references to heat acclimation are from the 18th century, coinciding with the emerging interests in colonization in tropical areas. There were deliberations of whether Europeans could adapt to live and work in the tropics. Luigi Westerna Sambon, in his address to the Royal Geographical Soc., London 1899, noted the possible deleterious effects of tropical infectious diseases and hygiene conditions, including “sunstroke... a condition that authors could prove a noxious influence of heat.” Although Dr Sambon thought that this is also an “infectious disease,” he clearly differentiated between fever and sunstroke (Siriasis—after Sirius that rises in the hottest month with the sun) and recognized that two important obstacles to acclimatization are heat (especially “if combined with moisture”) and diseases. Physiological experimentation on acclimatization to heat, only began at the start of the 20th century. In October 1926 and then in March–April 1927, there were fatal cases of heat stroke at City Deep mine, and Dr Aldo Dreosti was commissioned by Dr Orenstein, the chief medical officer of the Rand Gold Mines Company to conduct experiments to improve the adaptability of the workers to the underground environment of the mine. Dr Dreosti developed a heat tolerance test (HTT) using conditions that matched the underground heat and workload in the mine, and subsequently underground heat acclimation protocols to enhance heat tolerance corresponding with increased yield were introduced. In the review by Dr Suzanne M. Schneider “Heat Acclimation: Gold Mines and Genes” she describes an occupational scenario using several approaches to acclimate tens of thousands of workers allowing them to perform in the extreme conditions of high temperatures and 100% relative humidity with few fatalities. Although Dr Schneider reviewed the period between the 1890s and 1940, before mechanized tools and artificial cooling were introduced to the mine, she used Dreosti’s acclimation paradigms as a template to analyze the evolution of ideas regarding cost-effective heat acclimation and HTT procedures, which are still used today. In 1953, following increased cases of fatal heat stroke with deepening of the mining area, the Chamber of Mines funded research by C. Wyndham to improve acclimation protocols. Wyndham and Strydom (1973) (see in ref. 4) modified Dreosti’s program while using above-ground climatic chambers. Interestingly, the acclimation protocols used by both Dreosti and Wyndham were flexible and differentiated between heat-tolerant (adapted) and non-tolerant workers and thus assigned the new recruits to “personalized” acclimation protocols. Remarkably, the conclusion of both Dreosti’s and Wyndham’s protocols were that no differences in acclimation-performance capacity were noted among workers with different ethnicities or climatic origins. This conclusion fits with Nigel Taylorwho found no genetic differences in the ability to acclimate and attributed acclimatory changes to phenotypic adaptations. These findings also answered questions raised at the “Victorian debates” in 1899 of whether there are innate differences between the colonizers and those of the well-adapted natives. Given the 100% relative humidity in the mine, Dreosti only used Rectal Temperature (Tre) as a measure of tolerance, whereas Wyndham added cardiovascular and sweat rate parameters as strain criteria. To this end, HTT is used when a “return to duty verdict” in military troops is required. There are still debates regarding the best HTT protocol among troops.