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![Diagrammatic illustration of body temperature in the human body. a In cold environments, the area preserved at 37°C contracts and the shell area expands. b The body volume preserved at 37°C expands. Yellow areas in a, b, and c illustrate the " acral " regions that help control body temperature by constricting blood vessels when the body temperature falls. Arteriovenous anastomoses (AVA) found in the cutaneous vasculature of the acral regions open and close to allow or prevent, respectively, rapid heat loss from the skin. The concepts presented here are generalizations; a number of variables, such as gender, age, and individual difference can affect the temperature distribution (adapted from [10])](profile/Matthew-White-25/publication/51178470/figure/fig1/AS:394173648785408@1470989729106/Diagrammatic-illustration-of-body-temperature-in-the-human-body-a-In-cold-environments.png)
Diagrammatic illustration of body temperature in the human body. a In cold environments, the area preserved at 37°C contracts and the shell area expands. b The body volume preserved at 37°C expands. Yellow areas in a, b, and c illustrate the " acral " regions that help control body temperature by constricting blood vessels when the body temperature falls. Arteriovenous anastomoses (AVA) found in the cutaneous vasculature of the acral regions open and close to allow or prevent, respectively, rapid heat loss from the skin. The concepts presented here are generalizations; a number of variables, such as gender, age, and individual difference can affect the temperature distribution (adapted from [10])
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Many of the live human and animal vaccines that are currently in use are attenuated by virtue of their temperature-sensitive (TS) replication. These vaccines are able to function because they can take advantage of sites in mammalian bodies that are cooler than the core temperature, where TS vaccines fail to replicate. In this article, we discuss th...
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... understand the potential use of temperature-sensitive vaccines, one must appreciate the mechanisms of mammalian temperature regulation and the distribution of body temperatures. Human body temperatures vary noticeably from the deep visceral tissues and the central nervous system to the body surface ( Fig. 1). Even within the cranium from the third and fourth ventricles to the meninges there are centrifugal temperature gradients of up to 1°C [3,4]. In addition, within the airways there are pronounced variations of temperatures from the nares to the lower respiratory tract [5]. Irrespective of these regional variations, the core temperature ...
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... distribution of temperatures is best understood using a 2-compartment model of body temperatures [12]. The two compartments in this model are the shell and the core (Fig. ...
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... boundaries of these 2 compartments are indefinite and change according to ambient environmental conditions. At a cold ambient temperature (Fig. 1a), the surface temperatures are the lowest in the extremities (approximately 28-31°C) and the core compartment is regulated at 37°C. At warm ambient temperatures (Fig. 1b), two main changes are evident in the core and shell compartments. First, the physical size of the core compartment increases and the shell compartment decreases. ...
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... boundaries of these 2 compartments are indefinite and change according to ambient environmental conditions. At a cold ambient temperature (Fig. 1a), the surface temperatures are the lowest in the extremities (approximately 28-31°C) and the core compartment is regulated at 37°C. At warm ambient temperatures (Fig. 1b), two main changes are evident in the core and shell compartments. First, the physical size of the core compartment increases and the shell compartment decreases. Second, there is a reduction in the large gradient of surface temperatures evident in the cold (i.e., 28-31°C). In the cold (Fig. 1a), there is a pronounced peripheral ...
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... is regulated at 37°C. At warm ambient temperatures (Fig. 1b), two main changes are evident in the core and shell compartments. First, the physical size of the core compartment increases and the shell compartment decreases. Second, there is a reduction in the large gradient of surface temperatures evident in the cold (i.e., 28-31°C). In the cold (Fig. 1a), there is a pronounced peripheral vasoconstriction that physically increases the size of the shell compartment as warm blood is shifted to a smaller core compartment. In warm ambient conditions (Fig. 1b), more blood perfuses the vasodilated cutaneous vascular beds and the shell compartment physically expands in ...
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... decreases. Second, there is a reduction in the large gradient of surface temperatures evident in the cold (i.e., 28-31°C). In the cold (Fig. 1a), there is a pronounced peripheral vasoconstriction that physically increases the size of the shell compartment as warm blood is shifted to a smaller core compartment. In warm ambient conditions (Fig. 1b), more blood perfuses the vasodilated cutaneous vascular beds and the shell compartment physically expands in ...
Citations
... After validation of the developed models, a three-dimensional contour plot was obtained (known as a three-dimensional response surface) according to the mathematical analysis of the experimental data in order to visualise the interaction between different independent process variables and their impact on the four responses. The optimum process variables with LCST ranged between 28-32 • C near to the body surface temperature [42]; the highest value of G and t 50% , and the highest inhibition zone diameter, were identified. ...
Response surface methodology (RSM) was applied to optimise a temperature-responsive hydrogel formulation synthesised via the direct incorporation of biocellulose, which was extracted from oil palm empty fruit bunches (OPEFB) using the PF127 method. The optimised temperature-responsive hydrogel formulation was found to contain 3.000 w/v% biocellulose percentage and 19.047 w/v% PF127 percentage. The optimised temperature-responsive hydrogel provided excellent LCST near to the human body surface temperature, with high mechanical strength, drug release duration, and inhibition zone diameter against Staphylococcus aureus. Moreover, in vitro cytotoxicity testing against human epidermal keratinocyte (HaCaT) cells was conducted to evaluate the toxicity of the optimised formula. It was found that silver sulfadiazine (SSD)-loaded temperature-responsive hydrogel can be used as a safe replacement for the commercial SSD cream with no toxic effect on HaCaT cells. Last, but not least, in vivo (animal) dermal testing-both dermal sensitization and animal irritation-were conducted to evaluate the safety and biocompatibility of the optimised formula. No sensitization effects were detected on the skin applied with SSD-loaded temperature-responsive hydrogel indicating no irritant response for topical application. Therefore, the temperature-responsive hydrogel produced from OPEFB is ready for the next stage of commercialisation.
... The optimal temperature for Luc expression in mos-CHIK VRP-infected Vero cells was 34°C (Fig. 5), which is very close to the body surface temperature associated with the mosquito-borne transmission of the arbovirus (33). Note, however, that at 20 hpi, the optimal temperature for eGFP expression in mos-CHIK VRP-infected Vero cell was 28°C (Fig. 4A). ...
Chikungunya fever is a mosquito-transmitted infectious disease that induces rash, myalgia, and persistent incapacitating arthralgia. At present, no vaccines or antiviral therapies specific to Chikungunya virus (CHIKV) infection have been approved, and research is currently restricted to biosafety level 3 containment. CHIKV-like replicon particles (VRPs) are single-cycle infectious particles containing viral structure proteins, as well as a defective genome to provide a safe surrogate for living CHIKV to facilitate the testing of vaccines and antivirals. However, inefficient RNA transfection and the potential emergence of the competent virus through recombination in mammalian cells limit VRP usability. This study describes a transfection-free system for the safe packaging of CHIK VRP with all necessary components via transduction of mosquito cell lines using a single baculovirus vector. We observed the release of substantial quantities of mosquito cell-derived CHIK VRP (mos-CHIK VRP) from baculovirus-transduced mosquito cell lines. The VRPs were shown to recapitulate viral replication and subgenomic dual reporter expression (enhanced green fluorescent protein [eGFP] and luciferase) in infected host cells. Interestingly, the rapid expression kinetics of the VRP-expressing luciferase reporter (6 h) makes it possible to use mos-CHIK VRPs for the rapid quantification of VRP infection. Treatment with antivirals (suramin or 6-azauridine) or neutralizing antibodies (monoclonal antibodies [MAbs] or patient sera) was shown to inhibit mos-CHIK VRP infection in a dose-dependent manner. Ease of manufacture, safety, scalability, and high throughput make mos-CHIK VRPs a highly valuable vehicle for the study of CHIKV biology, the detection of neutralizing (NT) antibody activity, and the screening of antivirals against CHIKV. IMPORTANCE This study proposes a transfection-free system that enables the safe packaging of CHIK VRPs with all necessary components via baculovirus transduction. Those mosquito cell-derived CHIK VRP (mos-CHIK VRPs) were shown to recapitulate viral replication and subgenomic dual reporter (enhanced green fluorescent protein [eGFP] and luciferase) expression in infected host cells. Rapid expression kinetics of the VRP-expressing luciferase reporter (within hours) opens the door to using mos-CHIK VRPs for the rapid quantification of neutralizing antibody and antiviral activity against CHIKV. To the best of our knowledge, this is the first study to report a mosquito cell-derived alphavirus VRP system. Note that this system could also be applied to other arboviruses to model the earliest event in arboviral infection in vertebrates.
... This is particularly well documented in chronic autoimmune diseases such as rheumatoid arthritis (5,6). Even under normal circumstances, temperature is not consistent over time or across body locations and can fluctuate dramatically in extremities and in response to environmental conditions (7). While T cells are programmed to adapt to increasing temperatures through induction of a protective heatshock response (8) that may be induced in T cells at lower temperatures than other immune cells (9), the effect of heat and febrile temperatures on T cell metabolism and subsets remains poorly understood. ...
Heat is a cardinal feature of inflammation. Despite temperature variability and dependence of enzymes and complexes, how heat and fever affect immune cells remains uncertain. We found that heat broadly increased inflammatory activity of CD4 ⁺ T cell subsets and decreased Treg suppressive function. Th1 cells, however, also selectively developed mitochondrial dysfunction with high levels of ROS production and DNA damage. This led Th1 cells to undergo Tp53 -dependent death, which was required to minimize the accumulation of mutations in heat and inflammation. Th1 cells with similar DNA damage signatures were also detected in Crohn’s disease and rheumatoid arthritis. Fever and inflammation-associated heat thus selectively induce mitochondrial stress and DNA damage in activated Th1 cells that requires p53 to maintain genomic integrity of the T cell repertoire.
One Sentence Summary
Fever temperatures augment CD4 ⁺ T cell-mediated inflammation but induce differential metabolic stress and DNA damage in T cell subsets, with Th1 cells selectively sensitive and dependent on p53 to induce apoptosis and maintain genomic integrity.
... The temperature is measured at the arm as the patient feels comfortable measuring for long periods. Hence the temperature readings are recorded in the low-thirties [31]. The temperature in the outpatient ward is higher as the ward tends to have more people. ...
Telemedicine is a word that the world has been hearing about since the early days of the telephonic technology used to exchange information for delivering medical care. Medical practitioners need the holistic information of the patients to treat them effectively. Telemedicine is relatively limited compared to direct appointments; hence a prototype is needed to create an environment that is identical to the direct appointments where the practitioners can see the patient and their physiological data. A novel prototype with state-of-the-art software and hardware is developed for establishing a holistic telemedicine environment in this work. The designed system measures the skin temperature, SpO2, pulse rate, heart rate, breath rate, and Non-invasive Blood Pressure (NIBP). The SpO2 of the system is measured with Beer-Lambert’s law, and the NIBP is measured using a single synchronous ECG and PPG sensor. Quality video conferencing is provided between the patient and the practitioners.
... A physical feature of tissue microenvironments that can affect thermodynamic regulation of enzymatic rates and cell physiology is temperature (Fig. 1C). Temperatures fluctuate extensively in the human body, hovering around 37°C in the core and central organs, such as the spleen, to as low as 28°C in peripheral organs such as the skin at thermoneutrality [34,35]. Temperatures also vary widely in response to several physiological and pathophysiological mechanisms. ...
T cell metabolism is dynamic and highly regulated. While the intrinsic metabolic programs of T cell subsets are integral to their distinct differentiation and functional patterns, the ability of cells to acquire nutrients and cope with hostile microenvironments can limit these pathways. T cells must function in a wide variety of tissue settings, and how T cells interpret these signals to maintain an appropriate metabolic program for their demands or if metabolic mechanisms of immune suppression restrain immunity is an area of growing importance. Both in inflamed and cancer tissues, a wide range of changes in physical conditions and nutrient availability are now acknowledged to shape immunity. These include fever and increased temperatures, depletion of critical micro and macro-nutrients, and accumulation of inhibitory waste products. Here we review several of these factors and how the tissue microenvironment both shapes and constrains immunity.
... The sensor mounted over the skin surface responded to the skin temperature within 13 s, as shown in Fig. 4(b), and demonstrated the subject's skin temperature at different locations, such as the palm (33.5 • C), hand (33.7 • C), neck (35.6 • C), and forehead (36.6 • C), which was similar to the corresponding temperature measurements obtained by the thermal scanner. The outputs were reproduced for at least three different sets of sensors affixed at similar points, and displayed a temperature variation between 33.5 • C and 36.6 • C for the different skin locations of a subject tested at room temperature (29 • C) [45], [46]. It was observed that temperatures near the palm and hand were ∼33.5 • C, and the forehead region showed the highest temperature value of 36.6 • C. ...
Personalized mobile healthcare integrated with various wearable devices has become a significant area of interest in the present era. In the current research work, a flexible, wearable and disposable paper-based continuous skin temperature monitoring sensor for early medical prognosis and accurate diagnosis of body temperature-related ailments, such as COVID-19, is proposed. Conventional screen-printing and drop-casting techniques were used to fabricate the proposed sensor using MWCNTs as the sensing material and paper as the substrate. The linearity, stability, repeatability and durability of the sensors were tested from 29°C (room temperature) to 60°C. A thin sheet of PET was laminated over the sensor surface to ascertain its stability toward environmental effects and physical movements, and a response time of ~13 s and a recovery time of ~38 s with a sensitivity of −0.0685% °C
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were recorded. The efficacy of the proposed sensor was ascertained by placing it at different body locations on a human subject and comparing it with a standard thermocouple and IR sensor. The sensor even helped to effectively distinguish minimal temperature variations between various regions of the body. Furthermore, the feasibility of the fabricated temperature sensor as a temperature-based tactile sensor for robotics/artificial skin applications and as a noncontact breath monitoring device for use in personalized healthcare monitoring applications was investigated.
... In general, thermo-sensitive nanocarriers are designed to store their payloads at a physiological temperature of 37° C and when the temperature rises above 40-45 ° C, release the cargo quickly. Typically, pathophysiological conditions such as inflammation, infarction or tumor, as well as infections caused by microorganisms cause a local increase in temperature in the affected tissues [110,111]. Another temperature-responsive strategy is the concentrated 275 increase in temperature using external stimuli (e.g., ultrasound, magnetic field, etc.) that can be applied to the skin or can be done by irradiating metals in DDS that heat energy. Converts, remotely created. ...
Given that the production of a new drug molecule is time consuming and costly, pharmaceutical scientists seek to create a drug delivery system that is safe, effective, stable, and has good patient compliance. Targeted drug delivery is an advanced method of drug delivery that involves the controlled release of drugs at the target site (organs / tissues / cells) over a period of time. Targeted drug delivery is also known as smart or Intelligent drug delivery. In this method, the prescribed dose is reduced, which in turn improves the treatment by reducing the side effects of the drug. In designing such systems, important factors that should be considered are: Chemical and physical properties of drugs, Side effects or cytotoxicity for healthy cells, the route to be taken to deliver the medicine, the desired location, disease, Specific properties of target cells, the nature of markers or transport carriers or vehicles, which carry drugs to specific receptors and ligands and physically modulated components. The various drug carriers that can be used in this advanced delivery system include: Polymer-drug conjugates and nanoparticle systems such as Inorganic nanoparticles (e.g., magnetic nanoparticles, quantum dots), Dendrimers, liposomes and lipoproteins are monoclonal antibodies, microspheres, microemulsions and neutrophils, fibroblasts, artificial cells, micelles and immune micelles. These drug delivery systems are used in stem cell therapy, regeneration methods and cancer treatments. In this review article, the drug delivery system and the importance of targeting strategies as well as the basic aspects of targeted drug delivery were studied. Current approaches and future perspectives on clinical applications are also presented.
... Six were in the follicular phase of their menstrual cycle while the other three were in the luteal phase. Given that menstrual cycles are likely to alter core temperature [13], the menstrual cycle changes might not be followed by parallel changes in skin temperature [42]. ...
In order to determine the required duration of whole-body exposure to extreme cold (−110 °C) in males and females for achieving the same cold-induced response, a mathematical model of skin cooling kinetics was developed. This modeling is derived from the implementation of a new experimental cryotherapy protocol to obtain continuous skin temperature maps over time. Each 3-min whole-body cryostimulation session was divided into six incremental sessions of 30 s carried out over six consecutive days. Seventeen young, healthy subjects (8 males aged 22.6 +/-3.0 years and 9 females aged 23.7 +/-4.7 years) agreed to participate in this study. The smallest sex-related difference in temperature was found in the trunk area (2.93 °C after 3 min) while the greatest temperature drop was found in the lower limbs (5.92 °C after 3 min). The largest temperature variation was observed between the trunk and the lower limbs, and peaked at 2.67 °C in males and 6.99 °C in females. For both sexes, skin cooling kinetics showed a strong transient exponential type decrease followed by linear regression behavior. It appeared that for achieving the same cold-induced response, the required duration of cryostimulation is longer for males. For example, a trunk skin cooling of −12 °C could be achieved in 125s for females vs 170s for males (+36% longer); for the lower limbs, the same skin cooling magnitude could be reached after 87s for females vs 140s for males (+62% longer).
... Generally, mammalian cells grow optimally at 37 °C, and low temperatures, such as 33 °C used in our experiments, inhibit their growth [21]. As the surface temperature of the head and extremities is approximately 28-34 °C when exposed to low ambient temperatures [22], and there was decreased in LLC cell growth at 33 °C compared at 37 °C for 2 d ( Figure 3A), it was evident that low temperatures did not directly increase the growth of cancer cells. We used 33 °C as the temperature to study the effects of stromal cells on tumor cell growth in subsequent experiments ( Figure 3B). ...
... Generally, mammalian cells grow optimally at 37 • C, and low temperatures, such as 33 • C used in our experiments, inhibit their growth [21]. As the surface temperature of the head and extremities is approximately 28-34 • C when exposed to low ambient temperatures [22], and there was decreased in LLC cell growth at 33 • C compared at 37 • C for 2 d ( Figure 3A), it was evident that low temperatures did not directly increase the growth of cancer cells. We used 33 • C as the temperature to study the effects of stromal cells on tumor cell growth in subsequent experiments ( Figure 3B). ...
Ambient temperature can regulate the immune response and affect tumor growth. Although thermoneutral caging reduces tumor growth via immune activation, little attention has been paid to the tumorigenic effect of low temperature. In the present study, tumor growth was higher at low ambient temperature (4 °C for 8 h/d) than at the standard housing temperature (22 °C) in allograft models. Low temperature-stimulated tumor growth in mice was reduced by monocyte depletion using clodronate liposomes. Proliferation was considerably greater in cancer cells treated with 33 °C-cultured RAW264.7 cell-conditioned media (33CM) than in cells treated with 37 °C-cultured RAW264.7 cell-conditioned media (37CM). Additionally, glutamine levels were markedly higher in 33CM-treated cells than in 37CM-treated cells. We further confirmed that the addition of glutamine into 37CM enhanced its effects on cancer cell proliferation and glutamine uptake inhibition ameliorated the accelerated proliferation induced by 33CM. Consistently, the inhibition of glutamine uptake in the allograft model exposed to low temperature, effectively reduced tumor volume and weight. Collectively, these data suggest that the secretion and utilization of glutamine by macrophages and cancer cells, respectively, are key regulators of low temperature-enhanced cancer progression in the tumor microenvironment.
... Temperature sensitive strains are also ideal for vaccine development as they fail to grow at higher core temperatures of mammals, limiting their ability to infect hosts. Many live viral vaccines have used this property as a mechanism of attenuation [56]. M. paragordonae is a naturally temperature sensitive mycobacterial species that is unable to grow in temperatures above 37 • C, human's core temperature [50]. ...
Tuberculosis (TB) is the global leading cause of death from an infectious agent with approximately 10 million new cases of TB and 1.45 million deaths in 2018. Bacille Calmette-Guérin (BCG) remains the only approved vaccine for Mycobacterium tuberculosis (M. tb, causative agent of TB), however clinical studies have shown BCG has variable effectiveness ranging from 0-80% in adults. With 1.7 billion people latently infected, it is becoming clear that vaccine regimens aimed at both post-exposure and pre-exposure to M. tb will be crucial to end the TB epidemic. The two main strategies to improve or replace BCG are subunit and live attenuated vaccines. However, following the failure of the MVA85A phase IIb trial in 2013, more varied and innovative approaches are being developed. These include recombinant BCG strains, genetically attenuated M. tb and naturally attenuated mycobacteria strains, novel methods of immunogenic antigen discovery including for hypervirulent M. tb strains, improved antigen recognition and delivery strategies, and broader selection of viral vectors. This article reviews preclinical vaccine work in the last 5 years with focus on those tested against M. tb challenge in relevant animal models.
