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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])  

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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Article
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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

... 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. ...
Article
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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.
... 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. ...
Conference Paper
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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]. ...
Article
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). ...
Article
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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]. ...
Article
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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.
... Wireless thermal therapy of bacterial management has also been demonstrated to assist with wound healing. Previous studies have revealed that some bacteria are highly sensitive to environmental changes, and that an increase in temperature lowers their survival [94][95][96]. Figure 6c (left) shows a transient radio frequency (RF) device for thermal therapy based on the Mg heater, embedded between silk fibroin layers [97]. Figure 6c (right) reveals related implantation processes for rats. ...
Article
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Biodegradable and soft biomedical electronics that eliminate secondary surgery and ensure intimate contact with soft biological tissues of the human body are of growing interest, due to their emerging applications in high-quality healthcare monitoring and effective disease treatments. Recent systematic studies have significantly expanded the biodegradable electronic materials database, and various novel transient systems have been proposed. Biodegradable materials with soft properties and integration schemes of flexible or/and stretchable platforms will further advance electronic systems that match the properties of biological systems, providing an important step along the path towards clinical trials. This review focuses on recent progress and achievements in biodegradable and soft electronics for biomedical applications. The available biodegradable materials in their soft formats, the associated novel fabrication schemes, the device layouts, and the functionality of a variety of fully bioresorbable and soft devices, are reviewed. Finally, the key challenges and possible future directions of biodegradable and soft electronics are provided.
... For example parts of the human body, such as the skin on the arms and legs, remain below 37 C in all but the most extreme temperature and humidity conditions. Inoculation of TS vaccines at such sites allows for local replication of the microbe and the stimulation of an immune response that can include both humoral and T-cell responses [13,14]. ...
Article
Temperature sensitivity is often used as a way to attenuate micro-organisms to convert them into live vaccines. In this work, we explore the use of temperature-sensitive (TS) genetic circuits that express lethal genes as a widely applicable approach to TS attenuation. We tested different combinations of TS repressors and cognate promoters controlling the expression of genes encoding restriction endonucleases inserted at four different non-essential sites in the Escherichia coli chromosome. We found that the presence of the restriction endonuclease genes did not affect the viability of the host strains at the permissive temperature, but that expression of the genes at elevated temperatures killed the strains to varying extents. The chromosomal insertion site of the lethal cassettes affected their functionality, and insertion at one site, ycgH, rendered them ineffective at inducing death at high temperature. Induction of a TS circuit in a growing culture led to a reduced cell mass and a reduction of the number of cells that could exclude a dye that indicated viability. Incubation of cells carrying a TS lethal gene circuit initially grown at low temperature and then suspended in phosphate buffered saline at high temperature led to about 100-fold loss of cell viability per day, compared to a minimal loss of viability for the parental strain. Strains carrying either one or two TS lethal circuits could generate mutants that survived at high temperature. These mutants included complete deletions of the lethal gene circuits.
... The nanogels were fully characterized in terms of their hydrodynamic radius, cloud point temperature (T cp ), and the amount of the labeled dye (Table 1, Fig. S1, S2). The T cp of the nanogels was tuned to occur below the incubation temperature, which was set to 37°C to simulate the temperature of inflamed skin [38]. Based on previously reported studies [31] as confirmed in this work, the tNGs improved significantly the skin penetration of the encapsulated molecule which could be detected in higher amounts in the SC when the temperature of incubation was above the T cp (Fig. S3). ...
Article
In this paper we present a comprehensive study for the ability of thermoresponsive nanogels (tNG) to act as cutaneous penetration enhancers. Given the unique properties of such molecular architectures with regard to their chemical composition and thermoresponsive properties, we propose a particular mode of penetration enhancement mechanism, i.e. hydration of the stratum corneum. Different tNG were fabricated using dendritic polyglycerol as a multifunctional crosslinker and three different kinds of thermoresponsive polymers as linear counterpart: poly(N-isopropylacrylamide) (pNIPAM), p(di(ethylene glycol) methyl ether methacrylate - co - oligo ethylene glycol methacrylate) (DEGMA-co-OEGMA475), and poly(glycidyl methyl ether - co - ethyl glycidyl ether) (tPG). Excised human skin was investigated by means of fluorescence microscopy, which enabled the detection of significant increment in the penetration of tNG as well as the encapsulated fluorescein. The morphology of the treated skin samples was thoroughly investigated by transmission electron microscopy and stimulated Raman spectromicroscopy. We found that tNG can perturbate the organization of both proteins and lipids in the skin barrier, which was attributed to tNG hydration effects. Interestingly, different drug delivery properties were detected and the ability of each investigated tNG to enhance skin penetration correlated well with the degree of induced stratum corneum hydration. The differences in the penetration enhancements could be attributed to the chemical structures of the nanogels used in this study. The most effective stratum corneum hydration was detected for nanogels having additional or more exposed polyether structure in their chemical composition.
... A number of vaccine technologies have been applied in attempts to create new anti-tuberculosis vaccines, and many of these include ways of modifying BCG or attenuating M. tuberculosis (Bao et al. 2003;Sun et al. 2009;Grode et al. 2013;Tameris et al. 2013). Attenuation through temperature sensitivity (TS) is widely used to create live human viral vaccines and has been used to create some veterinary bacterial vaccines (White et al. 2011). If TS vaccine strains are appropriately constructed, they can be safe in even the most immunocompromised patients, as the core body temperature remains unchanged or elevated in diseased individuals. ...
Article
A synthetic version of the ligA gene encoding the NAD-dependent DNA ligase from the Arctic bacterium Pseudoalteromonas haloplanktis was substituted for its homologue in the chromosome of Mycobacterium smegmatis. The resulting recombinant strain grew identically to the parent strain at permissive temperatures but failed to grow above 37°C. The temperature-sensitive phenotype was stable, and the strain failed to generate temperature-resistant forms at a detectable level. Repeated passage of the hybrid strain resulted in no changes in the psychrophilic ligA gene. Given the high identity of the DNA ligases among mycobacterial species these results suggest that a stable temperature-sensitive strain of M. tuberculosis could be generated using the approach described here. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Article
While the recent literature on Whole-Body Cryotherapy pointed to its beneficial systemic effects on inflammatory markers in rheumatoid arthritis, it was not clear whether it could also have more localized effects, with the attainment of analgesic thresholds on hands that are usually protected during protocols. Twenty-five young, healthy subjects (12 males aged 25.1 ± 3.5 years and 13 females aged 23.5 ± 2.6 years) agreed to participate in this study. Two study groups were defined: (1) a control group with a hand fully gloved and (2) an experimental group with a partially ungloved hand during the WBC session. In both groups, the achievement of analgesic thresholds of skin temperature was established through thermal imaging, focused on the measurement of temperatures at the different joint locations. Using a new protocol with direct exposure of the hands during the last 40 s of a standard WBC session of 3 min at −110 °C made it possible to respect this risk/benefit balance. Infrared thermography analyses revealed that for all regions of interest (except MCP and IP, CMP for thumb), there was a clinically meaningful reduction of skin temperature in participants from the experimental group. The thermal analysis suggests that a protocol of Whole-Body Cryotherapy at −110 °C where hands must be ungloved during 40 s could be a useful tool for the management of hand rheumatoid arthritis by achieving local antalgic thresholds.