Reduction In Core Body Temperature Research Articles

Rifaximin alleviates intestinal barrier disruption and systemic inflammation via the PXR/NFκB/MLCK pathway and modulates intestinal Lachnospiraceae abundance in heat-stroke mice

Heatstroke is a critical condition with a high mortality rate and intestinal barrier dysfunction is a key factor in its progression to sepsis in some patients. This study aimed to explore the protective effects of rifaximin on the intestinal barrier in heat-stroke mice and the underlying mechanisms. A mouse model of heat stroke was established, followed by rifaximin intervention. Rifaximin significantly improved survival rates, reduced core body temperature, and alleviated intestinal tissue damage. Further mechanistic studies revealed that rifaximin restored heat stroke-induced damage to intestinal barrier function by upregulating the expression of the tight junction proteins, ZO-1 and occludin. Additionally, 16S rRNA sequencing showed that rifaximin significantly increased the abundance of Lachnospiraceae in the gut and enhanced short-chain fatty acid butyrate levels. In vitro experiment results revealed that butyrate promotes the expression of the intestinal epithelial cell protein MUC2, thereby strengthening the intestinal barrier. Rifaximin also activated the pregnane X receptor (PXR) signaling pathway and inhibited the NF-κB/MLCK signaling pathway, reducing the permeability of intestinal epithelial cells. This study demonstrated that rifaximin protects the intestinal barrier in mice with heat stroke through multiple pathways by modulating the gut microbiota, increasing butyrate production, and activating the PXR signaling pathway. These findings provide a new theoretical basis for the clinical application of rifaximin in heat stroke treatment.

Voluntary head dunking after exercise-induced hyperthermia rapidly reduces core body temperature in dogs.

To evaluate field-applicable cooling methods for treatment of exercise-induced hyperthermia in dogs. In this randomized, crossover study from June 27, 2023, to July 24, 2023, 12 working dogs exercised for 10 minutes until core body temperature reached 40.6 °C or above or ≥ 2 signs of heat stress were observed. Four different cooling protocols were evaluated: (1) neck chemical ice packs (2), (2) a wet (22 °C) neck towel, (3) wet (22 °C) axillae towels, or (4) voluntary head immersion ("dunking") into (22 °C) water. After intervention, dogs rested and were monitored for 40 minutes. The dunking protocol, which included limited water ingestion, produced the lowest mean core temperature in the initial 5 minutes after exercise, in the subsequent 35 minutes during which dogs cooled to baseline temperature and was the only protocol to prevent the initial postexercise temperature rise. All methods resulted in return to baseline temperature. Trained voluntary head dunk with limited water ingestion results in rapid cooling in field situations of exercise-induced hyperthermia in dogs with normal mental status and ability to pause panting. "Cool first, transport second" reduces morbidity and mortality of acute heat injury. When whole-body water immersion is not an option, the trained voluntary head dunk in mentally appropriate dogs prevents postexercise rise and rapidly reduces core body temperature within the first 5 minutes. Alternatively, allowing the dog to drink controlled amounts of cool water and pouring water on the dog's head may provide some benefit but warrants further study.

Impaired energy expenditure following exposure to either DDT or DDE in mice may be mediated by DNA methylation changes in brown adipose.

The insecticide dichlorodiphenyltrichloroethane (DDT) and its persistent metabolite, dichlorodiphenyldichloroethylene (DDE), have been associated with increased adiposity and obesity in multiple generations of rodents and humans. These lipophilic pollutants accumulate in adipose tissue and appear to decrease energy expenditure through the impairment of thermogenesis in brown adipose tissue (BAT). We hypothesized that impaired thermogenesis is due to persistent epigenetic modifications of BAT. To address this, we exposed C57BL/6 J mice to DDT or DDE from gestational day (GD) 11.5 to postnatal day (PND) 5, evaluated longitudinal body temperature, and performed reduced representation bisulfite sequencing and RNA sequencing of BAT from infant and adult offspring. Exposure to DDT or DDE reduced core body temperature in adult mice, and differential methylation at the pathway and gene level was persistent from infancy to adulthood. Furthermore, thermogenesis and biological pathways essential for thermogenic function, such as oxidative phosphorylation and mechanistic target of rapamycin kinase (mTOR) signaling, were enriched with differential methylation and RNA transcription in adult mice exposed to DDT or DDE. PAZ6 human brown preadipocytes were differentiated in the presence of DDT or DDE to understand the brown adipocyte-autonomous effect of these pollutants. In vitro exposure led to limited changes in RNA expression; however, mitochondrial membrane potential was decreased in vitro with 0.1 µM and 1 µM doses of DDT or DDE. These results demonstrate that concentrations of DDT and DDE relevant to human exposure have a significant effect on thermogenesis, the transcriptome, and DNA methylome of mouse BAT and the mitochondrial function of human brown adipocytes.

Catalpol alleviates heat stroke-induced liver injury in mice by downregulating the JAK/STAT signaling pathway

BackgroundHeat stroke (HS) generated liver injury is a lethal emergency that occurs when the body is exposed to temperatures up to 40 °C for a few hours. PurposeThis study aimed to evaluate the therapeutic prospects of Catalpol (CA) from the blood-cooling herb Rehamanniae Radix on liver injury by HS. Study design and methodsA murine HS model (41 ± 0.5 °C, 60 ± 5 % relative humidity) and two cell lines (lipopolysaccharide + 42 °C) were used to assess the protective effects of CA on physiological, pathological, and biochemical features in silico, in vivo, and in vitro. ResultsCA treatment significantly improved survival rates in vivo and cell viability in vitro over those of the untreated group. Additionally, CA treatment reduced core body temperature, enhanced survival time, and mitigated liver tissue damage. Furthermore, CA treatment also reduced the activities of AST and ALT enzymes in the serum samples of HS mice. Molecular docking analysis of the 28 overlapping targets between HS and CA revealed that CA has strong binding affinities for the top 15 targets. These targets are primarily involved in nine major signaling pathways, with the JAK-STAT pathway being highly associated with the other eight pathways. Our findings also indicate that CA treatment significantly downregulated the expression of proinflammatory cytokines both in vivo and in vitro while upregulating the expression of anti-inflammatory cytokines. Moreover, CA treatment reduced the levels of JAK2, phospho-STAT5, and phospho-STAT3 both in vivo and in vitro, which is consistent with its inhibition of the apoptotic markers p53, Bcl2, and Bax. ConclusionsHeat stroke-induced liver injury was inhibited by CA through the downregulation of JAK/STAT signaling.

Hypothalamic Neuromodulation and Control of the Dermal Surface Temperature of Livestock during Hyperthermia.

Hyperthermia elicits several physiological and behavioral responses in livestock to restore thermal neutrality. Among these responses, vasodilation and sweating help to reduce core body temperature by increasing heat dissipation by radiation and evaporation. Thermoregulatory behaviors such as increasing standing time, reducing feed intake, shade-seeking, and limiting locomotor activity also increase heat loss. These mechanisms are elicited by the connection between peripheral thermoreceptors and cerebral centers, such as the preoptic area of the hypothalamus. Considering the importance of this thermoregulatory pathway, this review aims to discuss the hypothalamic control of hyperthermia in livestock, including the main physiological and behavioral changes that animals adopt to maintain their thermal stability.

A preliminary study of the thermal strain experienced by dive support boat personnel

ABSTRACT Anecdotal evidence indicated some British military dive support boat personnel suffer from uncomfortably cold hands and feet, which could impair their performance and be associated with reductions in core body temperature. This study collected preliminary data on thermal stress and cognitive performance of personnel taking part in a cold-weather training exercise. Six men were monitored during four boat transits in a range of climatic conditions (air temperature +1.2°C to −10.5°C, wind chill −4.5°C to 19.3°C). Core body temperature was measured with a radio pill and 12 skin sites (ISO 9886 plus hand, finger, foot and toe) with iButtons or thermistors. Self-reported thermal comfort and thermal sensation was also recorded. Reaction time and selective attention were measured pre- and post-transit. Participants’ physical characteristics and personal clothing ensembles were recorded. No participant became hypothermic. Most participants’ hand, foot and digit temperatures fell to below 15°C, indicating a risk of impaired dexterity, in addition to that arising from gloves. During the trial, hand and digit temperatures occasionally fell below 10°C. The limited data collected showed personal clothing choices could provide adequate thermal protection for these conditions and temperatures, and highlighted inter-individual variation and the need to allow for significant variation of day-to-day environmental conditions.

Thermo regulated infant warming wrapper with infrared light emitting diodes for prevention of hypothermia in preterm low birth weight babies

Preterm born babies having low birth weight is subjected to heavy loss of heat due to inadequate fat deposit under their skin. This creates a reduction in core body temperature to below physiologically tolerable levels and eventually ends up in cold stress or hypothermia. In this paper, an improved method for providing a thermo neutral environment is provided making the best use of the thermal insulating properties of the polyethylene and polyurethane foam with embedded infrared light emitting diodes. Bench top testing shows the device has an average warming time of 15 minutes and retains the temperature to more than 24 hours. The warmer is tested to provide reliable operation for more than three-month period within which the baby is expected to gain normal weight. The efficacy, safety and performance of the device are tested as per international standards and results are produced. The wrapper can improve the healthcare of the new-born at large, especially for developing countries.

Increased Carbon Dioxide Respiration Prevents the Effects of Acceleration/Deceleration Elicited Mild Traumatic Brain Injury

Acceleration/deceleration forces are a common component of various causes of mild traumatic brain injury (mTBI) and result in strain and shear forces on brain tissue. A small quantifiable volume dubbed the compensatory reserve volume (CRV) permits energy transmission to brain tissue during acceleration/deceleration events. The CRV is principally regulated by cerebral blood flow (CBF) and CBF is primarily determined by the concentration of inspired carbon dioxide (CO2). We hypothesized that experimental hypercapnia (i.e. increased inspired concentration of CO2) may act to prevent and mitigate the actions of acceleration/deceleration-induced TBI. To determine these effects C57Bl/6 mice underwent experimental hypercapnia whereby they were exposed to medical-grade atmospheric air or 5% CO2 immediately prior to an acceleration/deceleration-induced mTBI paradigm. mTBI results in significant increases in righting reflex time (RRT), reductions in core body temperature, and reductions in general locomotor activity-three hours post injury (hpi). Experimental hypercapnia immediately preceding mTBI was found to prevent mTBI-induced increases in RRT and reductions in core body temperature and general locomotor activity. Ribonucleic acid (RNA) sequencing conducted four hpi revealed that CO2 exposure prevented mTBI-induced transcriptional alterations of several targets related to oxidative stress, immune, and inflammatory signaling. Quantitative real-time PCR analysis confirmed the prevention of mTBI-induced increases in mitogen-activated protein kinase kinase kinase 6 and metallothionein-2. These initial proof of concept studies reveal that increases in inspired CO2 mitigate the detrimental contributions of acceleration/deceleration events in mTBI and may feasibly be translated in the future to humans using a medical device seeking to prevent mTBI among high-risk groups.

1314-P: Activating GABAergic Neurons in the Caudal Preoptic Area Promote Energy Expenditure in Diet-Induced Obesity

Obesity results from the imbalance between energy intake and energy expenditure, which are tightly regulated by dynamic hypothalamic circuits. Our goal is to identify and leverage hypothalamic components that promote energy expenditure for successful weight loss. Vesicular communication by ventromedial hypothalamic nucleus (VMN) steroidogenic factor 1 (Sf1) neurons is required for maintaining body weight, due at least in part to stimulating metabolic activity in adipose tissue, but the mechanistic details are unclear. VMNSf1 neurons efferently communicate with relatively few places in the brain but the most prominent projections are in the most caudal regions of the preoptic area (cPOA) (+0.1 to -0.3mm bregma, lateral to the suprachiasmatic nucleus) . We tested the hypothesis that GABAergic cPOA neurons promote energy expenditure and weight loss by activating either GABAergic or glutamatergic neurons via hM3dq, using vGATCre (vesicular GABAergic transporter) or vGLUT2Cre (vesicular glutamatergic transporter 2) in diet-induced obese male mice. Activating vGATcPOA neurons reduced body weight and adiposity without altering food intake. Activating vGLUT2cPOA neurons reduced body weight and food intake but did not reduce adiposity. Activating vGLUT2cPOA neurons reduced core body temperature, but not vGATcPOA neurons. We are currently investigating the mechanisms for how vGATcPOA neurons reduce adiposity. Weight loss is not likely mediated by direct inhibition of vGLUT2cPOA neurons because diet induced obese male mice with CNO-initiated signaling of hM4di in vglut2cPOA neurons does not reduce adiposity or body weight. Alternatively, vGATcPOA neurons may communicate with a distinct efferent system. Indeed, vGATcPOA, but not vGLUT2cPOA, neurons project to the lateral hypothalamus and medial raphe. Future studies will reveal the functional connection between VMNSf1 neurons and vGATcPOA neurons, and the descending circuitry that promotes energy expenditure. Disclosure R.Basu: None. A.J.Elmendorf: Research Support; Eli Lilly and Company. C.A.Mahler: Stock/Shareholder; AstraZeneca, Pfizer Inc. J.Flak: Research Support; Eli Lilly and Company. Funding American Diabetes Association (17-INI-15) ; IU CDMD NIH/NIDDK (P30 DK097512)

Ketones Improve the Mitochondrial Coupling Efficiency of Brown Adipocytes

Brown adipose tissue (BAT) thermogenesis is an energy‐demanding response, and this capacity can be leveraged to dissipate excess energy in obesity and its associated metabolic complications. Therefore, understanding the regulatory mechanisms of BAT mitochondrial uncoupling and thermogenesis is crucial. Ketone bodies are endogenous metabolites mainly found during starvation and carbohydrate restriction; however, their regulatory role on BAT thermogenesis is elusive. In this study, we aim to investigate the potential metabolic reprogramming induced by ketones on BAT. We hypothesize that ketones are alternative fuels for BAT during energy/carbohydrate shortage and decrease mitochondrial uncoupling to counterbalance the systemic energy deficit. In mice, ketogenic diet reduces core body temperature by 0.4˚C. Using Seahorse respirometry in differentiated brown adipocytes, we found that ketones improve mitochondrial coupling efficiency (ATP‐linked respiration/ basal respiration) by 30%, implying an attempt to decrease thermogenesis. The gene Oxct1, encoding succinyl‐CoA:3‐ketoacid CoA transferase that is required for ketolysis, is abundantly expressed by brown adipocytes. BAT‐specific Oxct1 knockout renders mice more resistant to cold‐induced decrease in core body temperature during fasting or ketogenic diet, via mechanisms independent of UCP1. Together, our data suggest that ketones potentially communicate hunger to brown adipocytes, thus promoting mitochondrial coupling efficiency for energy conservation.

Dehydropiandrosterone (DHEA) reduces core body temperature and protects against heat stress intolerance in RYR1-T4826IHSI malignant hyperthermia susceptible mice

Severe heat stress is becoming a more frequent problem for both humans and animals as climate change progresses. Heat stress intolerance (HSI) is likely to have poorly understood genetic susceptibility factors. Expressed mutations in RYR1 confers intolerance is one of the best known monogenic causes of HSI that may be mediated by uncontrolled loss of Ca2+ from SR/ER stores in muscle fibers and possibly neurons. Dehydropiandrosterone (DHEA), an endogenous steroid hormone precursor, is one of the most abundant circulating steroids in humans.

Kisspeptin impacts on circadian and ultradian rhythms of core body temperature: Evidence in kisspeptin receptor knockout and kisspeptin knockdown mice

Kisspeptin is vital for the regulation of both fertility and metabolism. Kisspeptin receptor (Kiss1r) knockout (KO) mice exhibit increased adiposity and reduced energy expenditure in adulthood. Kiss1r mRNA is expressed in brown adipose tissue (BAT) and Kiss1r KO mice exhibit reduced Ucp1 mRNA in BAT and impaired thermogenesis. We hypothesised that mice with diminished kisspeptin signalling would exhibit reduced core body temperature (Tc) and altered dynamics of circadian and ultradian rhythms of Tc. Tc was recorded every 15-min over 14-days in gonadectomised wild-type (WT), Kiss1r KO, and also Kiss1-Cre (95% reduction in Kiss1 transcription) mice. Female Kiss1r KOs had higher adiposity and lower Ucp1 mRNA in BAT than WTs. No change was detected in Kiss1-Cre mice. Mean Tc during the dark phase was lower in female Kiss1r KOs versus WTs, but not Kiss1-Cre mice. Female Kiss1r KOs had a lower mesor and amplitude of the circadian rhythm of Tc than did WTs. In WT mice, there were more episodic ultradian events (EUEs) of Tc during the dark phase than the light phase, but this measure was similar between dark and light phases in Kiss1r KO and Kiss1-Cre mice. The amplitude of EUEs was higher in the dark phase in female Kiss1r KO and male Kiss1-Cre mice. Given the lack of clear metabolic phenotype in Kiss1-Cre mice, 5% of Kiss1 transcription may be sufficient for proper metabolic control, as was shown for fertility. Moreover, the observed alterations in Tc suggest that kisspeptin has a role in circadian and ultradian rhythm-driven pathways.

Evaluating Effect of Prophylactic Intravenous Dexamethasone in Post Spinal Shivering: A Single Centre Randomised Controlled Study

Introduction: Shivering is a common side effect of central neuraxial anaesthesia. Intravenous pethidine is commonly used in reducing shivering but has been associated with significant opioid side effects. Dexamethasone as a powerful anti-inflammatory and analgesia agent is postulated to inhibit inflammatory mediators’ release thus inhibiting central thermoregulatory centre, potentially attenuating post spinal shivering. This double-blinded randomised controlled study was to determine the ability of intravenous dexamethasone in decreasing the incidence, severity and the need for treatment for post spinal shivering.
 Methods: We recruited 72 patients requiring spinal anaesthesia and randomised them to receive either dexamethasone 0.1 mg/kg (up to 8 mg) or normal saline (placebo). We observed their tympanic membrane temperatures, mean arterial pressures and shivering scores at regular intervals up to 2 hours post-spinal or till end of surgery (minimum 30 minutes post spinal).
 Results: Both groups showed consistent and comparable drop in tympanic membrane temperatures and mean arterial pressures after spinal anaesthesia, except at 15 minutes in which patients of dexamethasone group demonstrated significantly higher temperatures than saline group (p=0.04). There were also significantly less patients in the dexamethasone group reporting incidence of visible shivering as compared to the placebo group (p=0.003). No significant difference was seen in severity of shivering or usage of pethidine.
 Conclusion: Dexamethasone has the potential to mitigate the reduction in core body temperature, especially at 15 minutes post spinal. It can reduce the incidence of clinically significant visible grade of shivering post spinal.

199-LB: ATF4 Deletion in Brown Adipose Tissue Impairs Adaptive Thermogenesis but Attenuates Diet-Induced Insulin Resistance

Short-term cold exposure induces the integrated stress response (ISR) and its main effector, the activating transcription factor 4 (ATF4), in brown adipose tissue (BAT). Furthermore, induction of ATF4 in BAT in response to mitochondrial stress is required for systemic metabolic adaptations mediated by BATokine secretion. To test the hypothesis that ATF4 in BAT is required for cold-induced thermogenesis and to promote BATokine secretion, we selectively deleted ATF4 in BAT by crossing Atf4 floxed mice with mice harboring the Cre recombinase under the control of the Ucp1 promoter (ATF4 BAT KO). KO mice experienced a significant reduction in core body temperature after 3 days of cold exposure relative to wild type (WT) mice. Impaired thermogenesis correlated with reduced BAT mass, and decreased UCP1 and tyrosine hydroxylase protein levels. In addition, KO mice had impaired cold-induced browning of white adipose tissue (WAT) and reduced expression of fibroblast growth factor 21 (Fgf21) and growth and differentiation factor 15 (Gdf15), BATokines shown to be induced in response to BAT thermogenic activation. Surprisingly, although KO mice had equivalent weight gain and fat mass relative to WT mice after 12 weeks of high-fat feeding, glucose and insulin intolerance were ameliorated, and fasting insulin levels were significantly reduced, indicating increased insulin sensitivity. Improved glucose clearance correlated with increased levels of glucose transporters 1 and 4 (GLUT1 and GLUT4) in BAT, but not in WAT or skeletal muscle. Taken together, our data indicate that Atf4 expression is required for full thermogenic activation of BAT and to regulate FGF21 and GDF15 release as BATokines, likely coordinating BAT thermogenesis with systemic adaptations. Finally, our data suggest that in diet-induced obesity, ATF4 downregulation may increase glucose utilization in BAT, contributing to improved glucose homeostasis and insulin sensitivity. Disclosure S. Bjorkman: None. A. A. Marti: None. E. T. Weatherford: None. L. M. García-peña: None. M. J. Potthoff: None. E. D. Abel: Board Member; Self; MyoKardia, Other Relationship; Self; AstraZeneca. R. Pereira: None. Funding National Institutes of Health (R01DK125405)

Irs2 deficiency alters hippocampus-associated behaviors during young adulthood

Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and insulin resistance, has been recognized as a risk factor for cognitive impairment and dementia, including Alzheimer’s disease (AD). Insulin receptor substrate2 (IRS2) is a major component of the insulin/insulin-like growth factor-1 signaling pathway. Irs2 deletion leads to life-threatening T2DM, promoting premature death in male mice regardless of their genetic background. Here, we showed for the first time that young adult male mice lacking Irs2 on a C57BL/6J genetic background (Irs2−/−/6J) survived in different experimental environments and displayed hippocampus-associated behavioral alterations. Young adult male Irs2−/−/6J mice also exhibit aberrant alterations in energy and nutrient sensors, such as AMP-activated protein kinase (AMPK) and glucose transporter3 (GLUT3), and reduced core body temperature accompanied by abnormal change in the temperature sensor in the brain. These results suggest that Irs2 deficiency-induced impairments of brain energy metabolism and thermoregulation contribute to hippocampus-associated behavioral changes in young adult male mice.

Exertional heat illness in Thoroughbred racehorses – Pathophysiology, case definition and treatment rationale

SummaryThe combination of extreme heat, humidity and strenuous exercise is potentially challenging to the thermoregulatory system of a Thoroughbred racehorse, and under certain circumstances can cause a condition called exertional heat illness (EHI). It is difficult to predict its occurrence in an individual animal due to the combination on race day of extrinsic and intrinsic risk factors. Education regarding EHI is essential to its prevention, and lack of understanding amongst those responsible for the horse’s care may in fact be the most important risk factor. The pathophysiology of EHI is similar across elite athletic species and is directly related to an elevation in core body temperature that exceeds the ‘critical thermal maximum’, causing widespread destruction of cells. It is not only the high core temperature but also its duration that will dictate outcome. Treatment strategies should decrease the hyperthermia to near normal levels within 30 min of onset, which will minimise adverse consequences. This review article outlines the pathophysiological changes as EHI progresses, and the case definition at each emergent level. Pharmacological treatment strategies and their rationale are presented. Aggressive cooling, however, is the key treatment and requires a technique which is both practical and effective in rapidly reducing core body temperature. The treatment paradigm is early detection, rapid assessment enabling prioritisation of individuals and aggressive cooling. Each stage is critically discussed.

Effects of manipulating body temperature on sleep in postmenopausal women

Study objectivesA decline in sleep quality, slow wave sleep (SWS) and slow wave activity (SWA) are common in older adults. Prior studies have shown that manipulating body temperature during sleep can increase SWS/SWA. The aim of this study was to determine the effects of manipulation of body temperatures during sleep, using a high heat capacity mattress, on SWS/SWA and heart rate in post-menopausal women. MethodsTwenty-four healthy postmenopausal women between 40 and 75 years of age (mean age 62.4 ± 8.2 years, mean BMI 25.4 ± 3.5 kg/m2) were randomized in a single-blind, counterbalanced, cross-over manner to sleep on either a high heat capacity mattress (HHCM) or a low heat capacity mattress (LHCM) a week apart. Sleep was recorded using polysomnography during an 8-h sleep opportunity. Core and peripheral temperature were recorded using an ingestible capsule and thermochron respectively. ResultsIn comparison to the LHCM, sleep on HHCM exhibited a selective increase in SWS (average increase in Stage N3 of 9.6 min (2.1%), p = 0.04) and in slow oscillatory (SO) activity (0.5–1 Hz) in the first NREM/REM cycle (p = 0.04). In addition, the HHCM induced a greater reduction in core body temperature (p = 0.002). The reduction in core body temperature (first 180 min after lights out) from LHCM to HHCM was associated (r = 0.5, p = 0.012) with the increase in SO activity (SO cycle 1 and 2/cycle 3 and 4). Average heart rate was 1.6 beats/minute lower across the night on the HHCM compared to the LHCM (p = 0.001). ConclusionsThe results of this study indicate that manipulation of body temperature during sleep may be a useful approach to enhance SWS sleep in postmenopausal women.

Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes.

Selenoproteins are a class of proteins with the selenium-containing amino acid selenocysteine (Sec) in their primary structure. Sec is incorporated into selenoproteins via recoding of the stop codon UGA, with specific cis and trans factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA[Ser]Sec, encoded in mice by the gene Trsp. Whole-body deletion of Trsp in mouse is embryonically lethal, while targeted deletion of Trsp in mice has been used to understand the role of selenoproteins in the health and physiology of various tissues. We developed a mouse model with the targeted deletion of Trsp in brown adipocytes (Trspf/f-Ucp1-Cre+/−), a cell type predominant in brown adipose tissue (BAT) controlling energy expenditure via activation of adaptive thermogenesis, mostly using uncoupling protein 1 (Ucp1). At room temperature, Trspf/f-Ucp1-Cre+/− mice maintain oxygen consumption and Ucp1 expression, with male Trspf/f-Ucp1-Cre+/− mice accumulating more triglycerides in BAT than both female Trspf/f-Ucp1-Cre+/− mice or Trspf/f controls. Acute cold exposure neither reduced core body temperature nor changed the expression of selenoprotein iodothyronine deiodinase type II (Dio2), a marker of adaptive thermogenesis, in Trspf/f-Ucp1-Cre+/− mice. Microarray analysis of BAT from Trspf/f-Ucp1-Cre+/− mice revealed glutathione S-transferase alpha 3 (Gsta3) and ELMO domain containing 2 (Elmod2) as the transcripts most affected by the loss of Trsp. Male Trspf/f-Ucp1-Cre+/− mice showed mild hypothyroidism while downregulating thyroid hormone-responsive genes Thrsp and Tshr in their BATs. In summary, modest changes in the BAT of Trspf/f-Ucp1-Cre +/− mice implicate a mild thyroid hormone dysfunction in brown adipocytes.

Impact of Intraoperative Hypothermia on Microsurgical Free Flap Reconstructions.

Patients requiring microsurgical defect reconstruction are highly susceptible to intraoperative hypothermia, given oftentimes long operative times and exposure of large skin surface areas. While the impact of hypothermia has been extensively studied across various surgical fields, its role in the setting of microsurgical free flap reconstruction remains elusive. This study evaluates the effects of hypothermia on outcomes of free flap reconstructions. Within 7 years, 602 patients underwent 668 microvascular free flap reconstructions. The cases were divided into two groups regarding the minimal core body temperature during free flap surgery: hypothermia (HT; < 36.0°C) versus normothermia (NT; ≥36.0°C). The data were retrospectively screened for patients' demographics, perioperative details, flap survival, surgical complications, and outcomes. Our data revealed no significant difference with regard to the rate of major and minor surgical complications, or the rate of revision surgery between both groups (p > 0.05). However, patients in the HT group showed significantly higher rates of total flap loss (6.6% [HT] vs. 3.0% [NT], p < 0.05) and arterial thrombosis (4.6% [HT] vs. 1.9% [NT], p < 0.05). This translated into a significantly longer hospitalization of patients with reduced core body temperature (HT: mean 16.8 days vs. NT: mean 15.1 days; p < 0.05). Hypothermia increases the risk for arterial thrombosis and total flap loss. While free flap transfer is feasible also in hypothermic patients, surgeons' awareness of core body temperature should increase. Taken together, we suggest that the mean intraoperative minimum temperature should range between 36 and 36.5°C during free flap surgery as a pragmatic guideline.

Postoperative Hypothermia in Surgical Patients at Azadi Teaching Hospital

Introduction: The sensation to cold, shake occurrence and shivering are events that are commonly developed following general anesthesia administration postoperatively. Hypothermia has been considered as the most frequent outcome of surgery underwent by anesthesia. Inadvertent hypothermia has been taken into account as common side effect in the postoperative period immediately and it is related to wide impairments and anomalies of different body organs. Concentration on predictive factors of hypothermia would be important to reduce the incidence rate and correct preventable unnecessary risks for patients in the health settings following surgical operations. The aim of study is to assess the magnitude and associated factors of postoperative hypothermia recovery room in patients underwent general anesthesia. Methods: A hospital based prospective cross-sectional study was conducted on200patients with different age groups of both genders who underwent a scheduled non-cardiac surgery and general anesthesia consecutively during the period between the October 1stand the November1st2016. Results: The study revealed that the overall core hypothermia in the study sample was31%. The study showed that the post-operative temperatures decreased statistically significantly in all study patients and separately in adults, children, males, or females P&lt;0.001. The study also revealed that the operation duration(p=0.045)and pre-operative temperature P&lt;0.001were predictors of post-operative hypothermia in study sample. Conclusions: The incidence of hypothermia among study sample was not so high. A significant reduction in core body temperature of patients between pre and post-operation times was found. Those patients with longer operation duration, lower room temperature, and lower pre-operative temperature were at more risk of post-operative hypothermia.