ResearchPad - body-temperature https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Why do biting horseflies prefer warmer hosts? tabanids can escape easier from warmer targets]]> https://www.researchpad.co/article/elastic_article_14494 Blood-sucking horseflies (tabanids) prefer warmer (sunlit, darker) host animals and generally attack them in sunshine, the reason for which was unknown until now. Recently, it was hypothesized that blood-seeking female tabanids prefer elevated temperatures, because their wing muscles are quicker and their nervous system functions better at a warmer body temperature brought about by warmer microclimate, and thus they can more successfully avoid the host’s parasite-repelling reactions by prompt takeoffs. To test this hypothesis, we studied in field experiments the success rate of escape reactions of tabanids that landed on black targets as a function of the target temperature, and measured the surface temperature of differently coloured horses with thermography. We found that the escape success of tabanids decreased with decreasing target temperature, that is escape success is driven by temperature. Our results explain the behaviour of biting horseflies that they prefer warmer hosts against colder ones. Since in sunshine the darker the host the warmer its body surface, our results also explain why horseflies prefer sunlit dark (brown, black) hosts against bright (beige, white) ones, and why these parasites attack their hosts usually in sunshine, rather than under shaded conditions.

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<![CDATA[Aging-associated sinus arrest and sick sinus syndrome in adult zebrafish]]> https://www.researchpad.co/article/elastic_article_13853 Because of its powerful genetics, the adult zebrafish has been increasingly used for studying cardiovascular diseases. Considering its heart rate of ~100 beats per minute at ambient temperature, which is very close to human, we assessed the use of this vertebrate animal for modeling heart rhythm disorders such as sinus arrest (SA) and sick sinus syndrome (SSS). We firstly optimized a protocol to measure electrocardiogram in adult zebrafish. We determined the location of the probes, implemented an open-chest microsurgery procedure, measured the effects of temperature, and determined appropriate anesthesia dose and time. We then proposed an PP interval of more than 1.5 seconds as an arbitrary criterion to define an SA episode in an adult fish at ambient temperature, based on comparison between the current definition of an SA episode in humans and our studies of candidate SA episodes in aged wild-type fish and Tg(SCN5A-D1275N) fish (a fish model for inherited SSS). With this criterion, a subpopulation of about 5% wild-type fish can be considered to have SA episodes, and this percentage significantly increases to about 25% in 3-year-old fish. In response to atropine, this subpopulation has both common SSS phenotypic traits that are shared with the Tg(SCN5A-D1275N) model, such as bradycardia; and unique SSS phenotypic traits, such as increased QRS/P ratio and chronotropic incompetence. In summary, this study defined baseline SA and SSS in adult zebrafish and underscored use of the zebrafish as an alternative model to study aging-associated SSS.

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<![CDATA[Exposure to dim light at night prior to conception attenuates offspring innate immune responses]]> https://www.researchpad.co/article/N231fece1-eb24-47b2-a00f-cbdce7a093c6

Functional circadian timekeeping is necessary for homeostatic control of the immune system and appropriate immune responsiveness. Disruption of natural light-dark cycles, through light at night (LAN), impairs innate and adaptive immune responses in nocturnal rodents. These altered immune responses are associated with disrupted endogenous gene transcriptional and endocrine cycles. However, few studies have addressed the multigenerational consequences of systemic circadian rhythm disruption. We hypothesized that parental exposure to dim LAN (dLAN) would alter innate immune and sickness responses to an endotoxin challenge in adult offspring gestated and reared in dark nights. Adult male and female Siberian hamsters were exposed to either dark nights (DARK) or dLAN (~5 lux) for 8 weeks, then paired, mated, and thereafter housed under dark nights. Maternal exposure to dLAN prior to conception impaired febrile responses and increased splenic il-1 production in response to LPS in male offspring. Paternal pre-conception dLAN dampened offspring tnf-α expression in the hypothalamus, reduced serum bactericidal capacity, and dark phase locomotor activity. These changes occurred despite offspring being conceived, gestated, and reared under standard dark night conditions. Overall, these data suggest that dLAN has intergenerational effects on innate immunity and sickness responses.

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<![CDATA[Pharmacokinetics of morphine in encephalopathic neonates treated with therapeutic hypothermia]]> https://www.researchpad.co/article/5c6f14b9d5eed0c48467a745

Objective

Morphine is a commonly used drug in encephalopathic neonates treated with therapeutic hypothermia after perinatal asphyxia. Pharmacokinetics and optimal dosing of morphine in this population are largely unknown. The objective of this study was to describe pharmacokinetics of morphine and its metabolites morphine-3-glucuronide and morphine-6-glucuronide in encephalopathic neonates treated with therapeutic hypothermia and to develop pharmacokinetics based dosing guidelines for this population.

Study design

Term and near-term encephalopathic neonates treated with therapeutic hypothermia and receiving morphine were included in two multicenter cohort studies between 2008–2010 (SHIVER) and 2010–2014 (PharmaCool). Data were collected during hypothermia and rewarming, including blood samples for quantification of morphine and its metabolites. Parental informed consent was obtained for all participants.

Results

244 patients (GA mean (sd) 39.8 (1.6) weeks, BW mean (sd) 3,428 (613) g, male 61.5%) were included. Morphine clearance was reduced under hypothermia (33.5°C) by 6.89%/°C (95% CI 5.37%/°C– 8.41%/°C, p<0.001) and metabolite clearance by 4.91%/°C (95% CI 3.53%/°C– 6.22%/°C, p<0.001) compared to normothermia (36.5°C). Simulations showed that a loading dose of 50 μg/kg followed by continuous infusion of 5 μg/kg/h resulted in morphine plasma concentrations in the desired range (between 10 and 40 μg/L) during hypothermia.

Conclusions

Clearance of morphine and its metabolites in neonates is affected by therapeutic hypothermia. The regimen suggested by the simulations will be sufficient in the majority of patients. However, due to the large interpatient variability a higher dose might be necessary in individual patients to achieve the desired effect.

Trial registration

www.trialregister.nl NTR2529.

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<![CDATA[Hygroregulation, a key ability for eusocial insects: Native Western European honeybees as a case study]]> https://www.researchpad.co/article/5c6730dbd5eed0c484f38231

Sociality has brought many advantages to various hymenoptera species, including their ability of regulating physical factors in their nest (e.g., temperature). Although less studied, humidity is known to be important for egg, larval and pupal development, and also for nectar concentration. Two subspecies of Apis mellifera of the M evolutionary lineage were used as models to test the ability of a superorganism (i.e. honeybee colony) to regulate the humidity in its nest (i.e. “hygroregulation hypothesis”) in four conservation centers: two in France (A. m. mellifera) and two in Portugal (A. m. iberiensis). We investigated the ability of both subspecies to regulate the humidity in hives daily, but also during the seasons for one complete year. Our data and statistical analysis demonstrated the capacity of the bees to regulate humidity in their hive, regardless of the day, season or subspecies. Furthermore, the study showed that humidity in beehives is stable even during winter, when brood is absent, and when temperature is known to be less stable in the beehives. These results suggest that humidity is important for honeybees at every life stage, maybe because of the ‘imprint’ of the evolutionary history of this hymenopteran lineage.

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<![CDATA[The influence of a hot environment on physiological stress responses in exercise until exhaustion]]> https://www.researchpad.co/article/5c648d4dd5eed0c484c824d1

Exhaustive exercise in a hot environment can impair performance. Higher epinephrine plasma levels occur during exercise in heat, indicating greater sympathetic activity. This study examined the influence of exercise in the heat on stress levels. Nine young healthy men performed a maximal progressive test on a cycle ergometer at two different environmental conditions: hot (40°C) and normal (22°C), both between 40% and 50% relative humidity. Venous blood and saliva samples were collected pre-test and post-test. Before exercise there were no significant changes in salivary biomarkers (salivary IgA: p = 0.12; α-amylase: p = 0.66; cortisol: p = 0.95; nitric oxide: p = 0.13; total proteins: p = 0.07) or blood lactate (p = 0.14) between the two thermal environments. Following exercise, there were significant increases in all variables (salivary IgA 22°C: p = 0.04, 40°C: p = 0.0002; α-amylase 22°C: p = 0.0002, 40°C: p = 0.0002; cortisol 22°C: p = 0.02, 40°C: p = 0.0002; nitric oxide 22°C: p = 0.0005, 40°C: p = 0.0003, total proteins 22°C: p<0.0001, 40°C: p<0.0001 and; blood lactate 22°C: p<0.0001, 40°C: p<0.0001) both at 22°C and 40°C. There was no significant adjustment regarding IgA levels between the two thermal environments (p = 0.74), however the levels of α-amylase (p = 0.02), cortisol (p<0.0001), nitric oxide (p = 0.02) and total proteins (p = 0.01) in saliva were higher in the hotter conditions. Blood lactate was lower under the hot environment (p = 0.01). In conclusion, enduring hot temperature intensified stressful responses elicited by exercise. This study advocates that hot temperature deteriorates exercise performance under exhaustive stress and effort conditions.

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<![CDATA[A match-day analysis of the movement profiles of substitutes from a professional soccer club before and after pitch-entry]]> https://www.researchpad.co/article/5c5ca2a2d5eed0c48441e7c0

Whilst the movement demands of players completing a whole soccer match have been well-documented, comparable information relating to substitutes is sparse. Therefore, this study profiled the match-day physical activities performed by soccer substitutes, focusing separately on the pre and post pitch-entry periods. Seventeen English Championship soccer players were monitored using 10 Hz Micromechanical Electrical Systems (MEMS) devices during 13 matches in which they participated as substitutes (35 observations). Twenty physical variables were examined and data were organised by bouts of warm-up activity (pre pitch-entry), and five min epochs of match-play (post pitch-entry). Linear mixed modelling assessed the influence of time (i.e., ‘bout’ and ‘epoch’), playing position, and match scoreline. Substitutes performed 3±1 rewarm-up bouts∙player-1∙match-1. Compared to the initial warm-up, each rewarm-up was shorter (-19.7 to -22.9 min) and elicited less distance (-606 to -741 m), whilst relative total distances were higher (+26 to +69 m∙min-1). Relative total (+13.4 m∙min-1) and high-speed (+0.4 m∙min-1) distances covered during rewarm-ups increased (p <0.001) with proximity to pitch-entry. Players covered more (+3.2 m; p = 0.047) high-speed distance per rewarm-up when the assessed team was losing compared with when winning at the time of pitch-entry. For 10 out of 20 variables measured after pitch-entry, values reduced from 0–5 min thereafter, and substitutes covered greater (p ˂0.05) total (+67 to +93 m) and high-speed (+14 to +33 m) distances during the first five min of match-play versus all subsequent epochs. Midfielders covered more distance (+41 m) per five min epoch than both attackers (p ˂0.001) and defenders (p = 0.016). Acknowledging the limitations of a solely movement data approach and the potential influence of other match-specific factors, such findings provide novel insights into the match-day demands faced by substitute soccer players. Future research opportunities exist to better understand the match-day practices of this population.

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<![CDATA[Chronic stress influences attentional and judgement bias and the activity of the HPA axis in sheep]]> https://www.researchpad.co/article/5c5b5295d5eed0c4842bcc05

Introduction

Environmental challenges are part of everyday life for most domestic animals. However, very little is known about how animals cope emotionally and physiologically with cumulative challenges. This experiment aimed to determine the impact of long-term exposure to environmental challenges on the affective state and hypothalamic-pituitary-adrenal (HPA) axis responses to a subsequent additional acute shearing challenge.

Methods

Sheep were exposed to either a long-term environmental challenge (rest disruption and individual housing) in order to induce chronic stress (chronic stress group) or control conditions (group housing in a field with low stress handling and daily feed rewards, control group). Judgement and attention bias were assessed as measures of the emotional state following several days of the challenge or control treatment (pre-shearing tests). In addition, the responsiveness of the HPA-axis was evaluated using a combined Corticotropin Releasing Hormone and Arginine Vasopressin (CRH/AVP) challenge. Finally, all animals were exposed to an acute shearing challenge, then judgement bias (post-shearing test), HPA-axis and internal body temperature responses were determined.

Results

In the pre-shearing judgement bias test, the chronic stress group slightly increased optimism compared to the control treatment. In the attention bias test, the chronic stress group showed reduced vigilance behaviour towards a predator threat and a quicker approach to the food compared to the control treatment. The chronic stress group also had lower plasma ACTH concentrations in response to the CRH/AVP challenge compared to the control group, no differences in cortisol concentrations were found. In the post-shearing judgement bias test, differences in optimism were no longer evident between the chronic stress and control groups. Plasma ACTH concentrations and body temperatures showed a greater increase in response to shearing in the chronic stress group compared to the control group.

Conclusion

Our results suggest that long-term exposure to challenges biased cognitive measures of the affective state towards an increased expectation of a reward and reduced attention towards a threat. The exaggerated ACTH responses in the chronic stress group may be indicative of HPA-axis dysregulation. Despite a period of challenge exposure in the chronic stress group, judgement bias responses to the shearing challenge were similar in the chronic stress and control groups; the reasons for this need further investigation. The altered affective state together with signs of HPA-axis dysregulation may indicate an increased risk of compromised welfare in animals exposed to long-term environmental challenges.

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<![CDATA[Association between temperature variability and daily hospital admissions for cause-specific cardiovascular disease in urban China: A national time-series study]]> https://www.researchpad.co/article/5c58d669d5eed0c484031dbb

Background

Epidemiological studies have provided compelling evidence of associations between ambient temperature and cardiovascular disease. However, evidence of effects of daily temperature variability on cardiovascular disease is scarce and mixed. We aimed to examine short-term associations between temperature variability and hospital admissions for cause-specific cardiovascular disease in urban China.

Methods and findings

We conducted a national time-series analysis in 184 cities in China between 2014 and 2017. Data on daily hospital admissions for ischemic heart disease, heart failure, heart rhythm disturbances, and ischemic stroke were obtained from the database of Urban Employee Basic Medical Insurance (UEBMI) including 0.28 billion enrollees. Temperature data were acquired from the China Meteorological Data Sharing Service Center. Temperature variability was calculated from the standard deviation (SD) of daily minimum and maximum temperatures over exposure days. City-specific associations between temperature variability and cardiovascular disease were examined with overdispersed Poisson models controlling for calendar time, day of the week, public holiday, and daily mean temperature and relative humidity. Random-effects meta-analyses were performed to obtain national and regional average associations. We also plotted exposure-response relationship curve using a natural cubic spline of temperature variability. There were 8.0 million hospital admissions for cardiovascular disease during the study period. At the national-average level, a 1-°C increase in temperature variability at 0–1 days (TV0–1) was associated with a 0.44% (0.32%–0.55%), 0.31% (0.20%–0.43%), 0.48% (0.01%–0.96%), 0.34% (0.01%–0.67%), and 0.82% (0.59%–1.05%) increase in hospital admissions for cardiovascular disease, ischemic heart disease, heart failure, heart rhythm disturbances, and ischemic stroke, respectively. The estimates decreased but remained significant when controlling for ambient fine particulate matter (PM2.5), NO2, and SO2 pollution. The main limitation of the present study was the unavailability of data on individual exposure to temperature variability.

Conclusions

Our findings suggested that short-term temperature variability exposure could increase the risk of cardiovascular disease, which may provide new insights into the health effects of climate change.

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<![CDATA[Environmental complexity: A buffer against stress in the domestic chick]]> https://www.researchpad.co/article/5c466559d5eed0c484518bb5

Birds kept in commercial production systems can be exposed to multiple stressors from early life and this alters the development of different morphological, immunological and behavioural indicators. We explore the hypothesis that provision of a complex environment during early life, better prepares birds to cope with stressful events as well as buffers them against future unpredictable stressful episodes. In this study, 96 one day old pullets were randomly distributed in eight pens (12 birds/pen). Half of the chicks (N = 48) were assigned to a Complex Environment (CENV: with perches, a dark brooder etc.) the others to a Simple Environment (SENV: without enrichment features). Half of the birds from each of these treatments were assigned to a No Stress (NSTR, 33°C) or to an acute Cold Stress (CSTR, 18–20°C) treatment during six hours on their second day of life. At four weeks of age, chicks with these four different backgrounds were exposed to an Intermittent Stressful Challenges Protocol (ISCP). In an immunological test indicative of pro-inflammatory status Phytohemagglutinin-P (PHA-P), the response of CSTR birds was ameliorated by rearing chicks in a CENV as they had a similar response to NSTR chicks and a significantly better pro-inflammatory response than those CSTR birds reared in a SENV (five days after the CSTR treatment was applied). A similar better response when coping with new challenges (the ISCP) was observed in birds reared in a CENV compared to those from a SENV. Birds reared in the CENV had a lower heterophil/lymphocyte ratio after the ISCP than birds reared in SENV, independently of whether or not they had been exposed to CSTR early in life. No effects of stress on general behaviour were detected, however, the provision of a CENV increased resting behaviour, which may have favoured stress recover. Additionally, we found that exposure to cold stress at an early age might have rendered birds more vulnerable to future stressful events. CSTR birds had lower humoral immune responses (sheep red blood cells induced antibodies) after the ISCP and started using elevated structures in the CENV later compared to their NSTR conspecifics. Our study reflects the importance of the early provision of a CENV in commercial conditions to reduce negative stress-related effects. Within the context of the theory of adaptive plasticity, our results suggest that the early experience of the birds had long lasting effects on the modulation of their phenotypes.

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<![CDATA[Machine learning methods for detecting urinary tract infection and analysing daily living activities in people with dementia]]> https://www.researchpad.co/article/5c478c95d5eed0c484bd3414

Dementia is a neurological and cognitive condition that affects millions of people around the world. At any given time in the United Kingdom, 1 in 4 hospital beds are occupied by a person with dementia, while about 22% of these hospital admissions are due to preventable causes. In this paper we discuss using Internet of Things (IoT) technologies and in-home sensory devices in combination with machine learning techniques to monitor health and well-being of people with dementia. This will allow us to provide more effective and preventative care and reduce preventable hospital admissions. One of the unique aspects of this work is combining environmental data with physiological data collected via low cost in-home sensory devices to extract actionable information regarding the health and well-being of people with dementia in their own home environment. We have worked with clinicians to design our machine learning algorithms where we focused on developing solutions for real-world settings. In our solutions, we avoid generating too many alerts/alarms to prevent increasing the monitoring and support workload. We have designed an algorithm to detect Urinary Tract Infections (UTI) which is one of the top five reasons of hospital admissions for people with dementia (around 9% of hospital admissions for people with dementia in the UK). To develop the UTI detection algorithm, we have used a Non-negative Matrix Factorisation (NMF) technique to extract latent factors from raw observation and use them for clustering and identifying the possible UTI cases. In addition, we have designed an algorithm for detecting changes in activity patterns to identify early symptoms of cognitive decline or health decline in order to provide personalised and preventative care services. For this purpose, we have used an Isolation Forest (iForest) technique to create a holistic view of the daily activity patterns. This paper describes the algorithms and discusses the evaluation of the work using a large set of real-world data collected from a trial with people with dementia and their caregivers.

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<![CDATA[Rationale for vaccination with trivalent or quadrivalent live attenuated influenza vaccines: Protective vaccine efficacy in the ferret model]]> https://www.researchpad.co/article/5c0ed794d5eed0c484f1441b

Background and aim

The majority of seasonal influenza vaccines are trivalent, containing two A virus strains (H1N1 and H3N2) and one B virus strain. The co-circulation of two distinct lineages of B viruses can lead to mismatch between the influenza B virus strain recommended for the trivalent seasonal vaccine and the circulating B virus. This has led some manufacturers to produce quadrivalent influenza vaccines containing one strain from each B lineage in addition to H1N1 and H3N2 strains. However, it is also important to know whether vaccines containing a single influenza B strain can provide cross-protectivity against viruses of the antigenically distinct lineage. The aim of this study was to assess in naïve ferrets the potential cross-protective activity of trivalent live attenuated influenza vaccine (T-LAIV) against challenge with a heterologous wild-type influenza B virus belonging to the genetically different lineage and to compare this activity with effectiveness of quadrivalent LAIV (Q-LAIV) in the ferret model.

Methods and results

Ferrets were vaccinated with either one dose of trivalent LAIV containing B/Victoria or B/Yamagata lineage virus, or quadrivalent LAIV (containing both B lineages), or placebo. They were then challenged with B/Victoria or B/Yamagata lineage wild-type virus 28 days after vaccination. The ferrets were monitored for clinical signs and morbidity. Nasal swabs and lung tissue samples were analyzed for the presence of challenge virus. Antibody response to vaccination was assessed by routine hemagglutination inhibition assay. All LAIVs tested were found to be safe and effective against wild-type influenza B viruses based on clinical signs, and virological and histological data. The absence of interference between vaccine strains in trivalent and quadrivalent vaccine formulations was confirmed. Trivalent LAIVs were shown to have the potential to be cross-protective against infection with genetically different influenza B/Victoria and B/Yamagata lineages.

Conclusions

In this ferret model, quadrivalent vaccine provided higher protection to challenge against both B/Victoria and B/Yamagata lineage viruses. However, T-LAIV provided some cross-protection in the case of a mismatch between circulating and vaccine type B strains. Notably, B/Victoria-based T-LAIV was more protective compared to B/Yamagata-based T-LAIV.

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<![CDATA[Effects of cold on murine brain mitochondrial function]]> https://www.researchpad.co/article/5c12cf83d5eed0c4849147f5

Therapeutic hypothermia is a strategy that reduces metabolic rate and brain damage during clinically-relevant hypoxic events. Mitochondrial respiration is compromised by hypoxia, with deleterious consequences for the mammalian brain; however, little is known about the effects of reduced temperature on mitochondrial metabolism. Therefore, we examined how mitochondrial function is impacted by temperature using high resolution respirometry to assess electron transport system (ETS) function in saponin-permeabilized mouse brain at 28 and 37°C. Respirometric analysis revealed that, at the colder temperature, ETS respiratory flux was ~ 40–75% lower relative to the physiological temperature in all respiratory states and for all fuel substrates tested. In whole brain tissue, the enzyme maximum respiratory rates for complexes I-V were similarly reduced by between 37–88%. Complexes II and V were particularly temperature-sensitive; a temperature-mediated decrease in complex II activity may support a switch to complex I mediated ATP-production, which is considerably more oxygen-efficient. Finally, the mitochondrial H+-gradient was more tightly coupled, indicating that mitochondrial respiration is more efficient at the colder temperature. Taken together, our results suggest that improvements in mitochondrial function with colder temperatures may contribute to energy conservation and enhance cellular viability in hypoxic brain.

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<![CDATA[Behavioral thermoregulation in Locusta migratoria manilensis (Orthoptera: Acrididae) in response to the entomopathogenic fungus, Beauveria bassiana]]> https://www.researchpad.co/article/5c0841aed5eed0c484fca706

Insects such as locusts and grasshoppers can reduce the effectiveness of pathogens and parasites by adopting different defense strategies. We investigated the behavioral thermopreference of Locusta migratoria manilensis (Meyen) (Orthoptera: Acrididae) induced by the fungus Beauveria bassiana, and the impact this behavior had on the fungal mycosis under laboratory conditions. By basking in higher temperature locations, infected nymphs elevated their thoracic temperature to 30–32.6 °C, which is higher than the optimum temperature (25°C) for B. bassiana conidial germination and hyphal development. A minimum thermoregulation period of 3 h/day increased survival of infected locusts by 43.34%. The therapeutic effect decreased when thermoregulation was delayed after initial infection. The fungus grew and overcame the locusts as soon as the thermoregulation was interrupted, indicating that thermoregulation helped the insects to cope with infection but did not completely rid them of the fungus. A significant enhancement in the number of haemocytes was observed in infected thermoregulating locusts, reaching levels that were even higher than those observed in the controls. In contrast, haemocyte concentration was severely reduced in infected insects that did not thermoregulate. In infected non-thermoregulating locusts, the reduction in haemocyte number was accompanied by an increase in fungal blastospore concentration that was obvious in the haemolymph by day four. In contrast, no circulating blastospores were found in the haemolymph of infected thermoregulating locusts three days post-inoculation. We also examined the phagocytic activity of infected insects in vivo by using fluorescein isothiocyanate (FITC)-labelled silica beads. The proportion of beads that was engulfed by haemocytes in infected, thermoregulating insects was similar to that in the controls throughout the experiment, whereas the rate of phagocytosis in infected, non-thermoregulating insects progressively decreased after infection. These findings demonstrated that behavioural thermoregulation can adversely affect B. bassiana mycosis in infected L. migratoria manilensis, thereby limiting the development of lethal entomopathogenic fungi in locusts. This is apparently accomplished through an increase in the levels of haemocytes, leading to greater phagocytic activity under certain environmental conditions.

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<![CDATA[Anesthesia-Induced Hypothermia Attenuates Early-Phase Blood-Brain Barrier Disruption but Not Infarct Volume following Cerebral Ischemia]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdcbe7

Blood-brain barrier (BBB) disruption is thought to facilitate the development of cerebral infarction after a stroke. In a typical stroke model (such as the one used in this study), the early phase of BBB disruption reaches a peak 6 h post-ischemia and largely recovers after 8–24 h, whereas the late phase of BBB disruption begins 48–58 h post-ischemia. Because cerebral infarct develops within 24 h after the onset of ischemia, and several therapeutic agents have been shown to reduce the infarct volume when administered at 6 h post-ischemia, we hypothesized that attenuating BBB disruption at its peak (6 h post-ischemia) can also decrease the infarct volume measured at 24 h. We used a mouse stroke model obtained by combining 120 min of distal middle cerebral arterial occlusion (dMCAo) with ipsilateral common carotid arterial occlusion (CCAo). This model produced the most reliable BBB disruption and cerebral infarction compared to other models characterized by a shorter duration of ischemia or obtained with dMCAO or CCAo alone. The BBB permeability was measured by quantifying Evans blue dye (EBD) extravasation, as this tracer has been shown to be more sensitive for the detection of early-phase BBB disruption compared to other intravascular tracers that are more appropriate for detecting late-phase BBB disruption. We showed that a 1 h-long treatment with isoflurane-anesthesia induced marked hypothermia and attenuated the peak of BBB disruption when administered 6 h after the onset of dMCAo/CCAo-induced ischemia. We also demonstrated that the inhibitory effect of isoflurane was hypothermia-dependent because the same treatment had no effect on ischemic BBB disruption when the mouse body temperature was maintained at 37°C. Importantly, inhibiting the peak of BBB disruption by hypothermia had no effect on the volume of brain infarct 24 h post-ischemia. In conclusion, inhibiting the peak of BBB disruption is not an effective neuroprotective strategy, especially in comparison to the inhibitors of the neuronal death signaling cascade; these, in fact, can attenuate the infarct volume measured at 24 h post-ischemia when administered at 6 h in our same stroke model.

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<![CDATA[Optimization and evaluation of astragalus polysaccharide injectable thermoresponsive in-situ gels]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc195

The objective of this study was to develop an injectable in situ forming gel system based on Poloxamer for sustained release of Astragalus polysaccharide (APS), thus achieved once or twice administration instead of frequent dosing during long-term treatment. The optimal formulation is 10 g APS, 18 g poloxamer 407, 2 g poloxamer 188, 0.15 g CMC-Na, 0.85 g sodium chloride in 100 ml gel in situ which had a preferable sol-gel transition temperature(T sol-gel) (34.1 ± 0.4°C), and good stability. In vitro release studies, all formulations containing polymer additives had prolonged release time and decreased initial burst to some extent. The optimal formulation containing 0.15% CMC-Na showed a best sustained release profile for about 132 h with the lowest initial burst in vitro about 16.30% in 12 h). In vivo, Male BALB/c mice (18–20 g) were administrated with APS in-situ gel just once, the values of immune organ indices, spleen lymphocyte proliferation, and serum IgM, IgG, IL-2 and IL-6 had significant increase, which was consistent with the mice given daily APS injections (7 times), while the above indices were increased more significantly in which administrated with APS in-situ gel twice. Based on these results, it can be concluded that the Poloxamer depot is a promising carrier for the sustained release of APS with an ideal release behavior.

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<![CDATA[Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model]]> https://www.researchpad.co/article/5989da7dab0ee8fa60b994ca

Background

Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma.

Materials & Methods

Male pigs (35 ± 5kg) were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min). After resuscitation, hypothermia (33°C) was induced for a period of 12 h (HT-T group) with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma) cytokine levels (IL-6, -8, -10) and alarmins (HMGB1, HSP70) were measured via ELISA.

Results

Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h.

Conclusion

A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application.

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<![CDATA[Does Whole-Body Hypothermia in Neonates with Hypoxic–Ischemic Encephalopathy Affect Surfactant Disaturated-Phosphatidylcholine Kinetics?]]> https://www.researchpad.co/article/5989da3fab0ee8fa60b89496

Background

It is unknown whether Whole-Body Hypothermia (WBH) affects pulmonary function. In vitro studies, at relatively low temperatures, suggest that hypothermia may induce significant changes to the surfactant composition. The effect of WBH on surfactant kinetics in newborn infants is unknown. We studied in vivo kinetics of disaturated-phosphatidylcholine (DSPC) in asphyxiated newborns during WBH and in normothermic controls (NTC) with no or mild asphyxia. Both groups presented no clinically apparent lung disease.

Methods

Twenty-seven term or near term newborns requiring mechanical ventilation were studied (GA 38.6±2.2 wks). Fifteen during WBH and twelve NTC. All infants received an intra-tracheal dose of 13C labelled DSPC and tracheal aspirate were performed. DSPC amount, DSPC half-life (HL) and pool size (PS) were calculated.

Results

DSPC amount in tracheal aspirates was 0.42 [0.22–0.54] and 0.36 [0.10–0.58] mg/ml in WBH and NTC respectively (p = 0.578). DSPC HL was 24.9 [15.7–52.5] and 25.3 [15.8–59.3] h (p = 0.733) and DSPC PS was 53.2 [29.4–91.6] and 40.2 [29.8–64.6] mg/kg (p = 0.598) in WBH and NTC respectively.

Conclusions

WBH does not alter DSPC HL and PS in newborn infants with no clinical apparent lung disease.

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<![CDATA[Bioelectrical impedance vector analysis (BIVA) for measuring the hydration status in young elite synchronized swimmers]]> https://www.researchpad.co/article/5989db5dab0ee8fa60be0403

Purpose

The assessment of body hydration is a complex process, and no measurement is valid for all situations. Bioelectrical impedance vector analysis (BIVA) has emerged as a relatively novel technique for assessing hydration status in sports. We applied BIVA a) to determine hydration changes evoked by an intense synchronized swimming (SS) training session; b) to characterize the sample of young elite swimmers in relation with a nonathletic reference population; and c) to generate its 50%, 75% and 95% percentiles of the bioelectrical variables.

Methods

Forty-nine elite SS female swimmers of two age categories, comen (Co: 13.9 ± 0.9 years, n = 34) and junior (Jr: 16.3 ± 0.6 years, n = 15), performed a long, high intensity training session. Body mass (BM) and bioelectrical variables (R, resistance; Xc, reactance; PA, phase angle; and Z, impedance module) were assessed pre- and post-training. BIVA was used to characterize 1) the distribution pattern of the bioelectrical vector (BIA vector) for both age groups, and 2) pre- to post-training BIA vector migration. Bioelectrical variables were also correlated with BM change values.

Results

Most swimmers were mostly located outside the 75% and some beyond the 95% percentile of the bioelectrical tolerance ellipses of the general population. The BIA vector showed statistically significant differences in both Co (T2 = 134.7, p = 0.0001) and Jr (T2 = 126.2, p < 0.001). Both groups were also bioelectrically different (T2 = 17.6, p < 0.001). After the training session, a decrease in BM (p = 0.0001) and an increase in BIA variables (p = 0.01) was observed. BIVA also showed a significant pre-post vector migration both in Co (T2 = 82.1; p < 0.001) and Jr (T2 = 41.8; p < 0.001). No correlations were observed between BM changes and bioelectrical variables.

Conclusions

BIVA showed specific bioelectrical characteristics in young elite SS athletes. Considering the decrease in BM and the migration of the BIA vector, we conclude that the homeostatic hydration status of these young elite female swimmers was affected by the execution of intense training sessions. From a methodological perspective, BIVA appears to be sensitive enough to detect subtle hydration changes, but further research is needed to ensure its validity and reliability. Moreover, these findings highlight the importance of ensuring adequate fluid intake during training in young SS athletes.

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<![CDATA[Hypothalamic Temperature of Rats Subjected to Treadmill Running in a Cold Environment]]> https://www.researchpad.co/article/5989dafbab0ee8fa60bc49fe

Different strategies for cooling the body prior to or during physical exercise have been shown to improve prolonged performance. Because of ethical and methodological issues, no studies conducted in humans have evaluated the changes in brain temperature promoted by cooling strategies. Therefore, our first aim sought to measure the hypothalamic temperature (Thyp) of rats subjected to treadmill running in a cold environment. Moreover, evidence suggests that Thyp and abdominal temperature (Tabd) are regulated by different physiological mechanisms. Thus, this study also investigated the dynamics of exercise-induced changes in Thyp and Tabd at two ambient temperatures: 25°C (temperate environment) and 12°C (cold). Adult male Wistar rats were used in these experiments. The rats were implanted with a guide cannula in the hypothalamus and a temperature sensor in the abdominal cavity. After recovery from this surgery, the rats were familiarized with running on a treadmill and were then subjected to the two experimental trials: constant-speed running (20 m/min) at 12°C and 25°C. Both Thyp and Tabd increased during exercise at 25°C. In contrast, Thyp and Tabd remained unchanged during fatiguing exercise at 12°C. The temperature differential (i.e., Thyp - Tabd) increased during the initial min of running at 25°C and thereafter decreased toward pre-exercise values. Interestingly, external cooling prevented this early increase in the temperature differential from the 2nd to the 8th min of running. In addition, the time until volitional fatigue was higher during the constant exercise at 12°C compared with 25°C. Together, our results indicate that Thyp and Tabd are regulated by different mechanisms in running rats and that external cooling affected the relationship between both temperature indexes observed during exercise without environmental thermal stress. Our data also suggest that attenuated hypothalamic hyperthermia may contribute to improved performance in cold environments.

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