Reversible Switching Between Microwave Absorption and EMI Shielding of VO2 Composite Foam.

Developing lightweight composite with reversible switching between microwave (MW) absorption and electromagnetic interference (EMI) shielding is promising yet remains highly challenging due to the completely inconsistent attenuation mechanism for electromagnetic (EM) radiation. Here, a lightweight vanadium dioxide/expanded polymer microsphere composites foam (VO2/EPM) is designed and fabricated with porous structures and 3D VO2 interconnection, which possesses reversible switching function between MW absorption and EMI shielding under thermal stimulation. The VO2/EPM exhibits MW absorption with a broad effective absorption bandwidth of 3.25 GHz at room temperature (25 °C), while provides EMI shielding of 23.1 dB at moderately high temperature (100 °C). This reversible switching performance relies on the porous structure and tunability of electrical conductivity, complex permittivity, and impedance matching, which are substantially induced by the convertible crystal structure and electronic structure of VO2. Finite element simulation is employed to qualitatively investigate the change in interaction between EM waves and VO2/EPM before and after the phase transition. Moreover, the application of VO2/EPM is demonstrated with a reversible switching function in controlling wireless transmission on/off, showcasing its excellent cycling stability. This kind of smart material with a reversible switching function shows great potential in next-generation electronic devices.

Cold stimulation is feasible and has limited aversiveness in healthy, pain-free dogs.

OBJECTIVE: The study aimed to evaluate the applicability and repeatability of cold stimulation in dogs. ANIMALS: 10 healthy Beagle dogs were used in a blinded cross-over experiment. METHODS: Measurements were performed in triplicate at 4 skin locations. The probe was manually placed, and temperature decreased (32 to 10 °C) at different cooling rates (0.5, 1, and 5 °C second-1) and latency was measured (11 °C for 60 seconds). Stimulations were discontinued when avoidance reactions were detected. Thermal threshold or time-to-reaction were recorded. Experiments were performed 3 times per animal in weeks 1 (Exp1), 2 (Exp2), and 5 (Exp3). Feasibility of cold stimulation was scored (0-5). Data were analyzed with mixed logistic regression. RESULTS: No significant differences in number of avoidance reactions between cooling-rates were detected. Significantly more reactions (P < .001) were observed during Exp1 compared to Exp2 and Exp3. Thermal thresholds were 13 ± 2.6 °C, 17.7 ± 4 °C and 16.3 ± 4.6 °C for 5, 0.5 and 1 °C second-1, respectively. Latency to the reaction was determinable in 37% of measurements. The mean time-to-reaction was 13 ± 11 seconds. In 85% of measurements, a feasibility score of 0 (best feasibility) was assigned. CLINICAL RELEVANCE: The method is easily applicable and well tolerated, but habituation could not be excluded. Overall, the aversiveness of cold stimulation in healthy dogs is limited and it is not possible to recommend a specific protocol. In future studies, it needs to be determined if the aversiveness of cold stimulation is increased in diseased dogs.

Differential Effects of Thermal Stimuli in Eliciting Temporal Contrast Enhancement: A Psychophysical Study.

Offset analgesia (OA) is observed when pain relief is disproportional to the reduction of noxious input and is based on temporal contrast enhancement (TCE). This phenomenon is believed to reflect the function of the inhibitory pain modulatory system. However, the mechanisms contributing to this phenomenon remain poorly understood, with previous research focusing primarily on painful stimuli and not generalizing to nonpainful stimuli. Therefore, the aim of this study was to investigate whether TCE can be induced by noxious as well as innocuous heat and cold stimuli. Asymptomatic subjects (n = 50) were recruited to participate in 2 consecutive experiments. In the first pilot study (n = 17), the parameters of noxious and innocuous heat and cold stimuli were investigated in order to implement them in the main study. In the second (main) experiment, subjects (n = 33) participated in TCE paradigms consisting of 4 different modalities, including noxious heat (NH), innocuous heat (IH), noxious cold (NC), and innocuous cold (IC). The intensity of the sensations of each thermal modality was assessed using an electronic visual analog scale. TCE was confirmed for NH (P < .001), NC (P = .034), and IC (P = .002). Conversely, TCE could not be shown for IH (P = 1.00). No significant correlation between TCE modalities was found (r < .3, P > .05). The results suggest that TCE can be induced by both painful and nonpainful thermal stimulation but not by innocuous warm temperature. The exact underlying mechanisms need to be clarified. However, among other potential mechanisms, this may be explained by a thermo-specific activation of C-fiber afferents by IH and of A-fiber afferents by IC, suggesting the involvement of A-fibers rather than C-fibers in TCE. More research is needed to confirm a peripheral influence. PERSPECTIVE: This psychophysical study presents the observation of temporal contrast enhancement during NH, NC, and innocuous cold stimuli but not during stimulation with innocuous warm temperatures in healthy volunteers. A better understanding of endogenous pain modulation mechanisms might be helpful in explaining the underlying aspects of pain disorders.

Membrane Order Effect on the Photoresponse of an Organic Transducer.

Non-genetic photostimulation, which allows for control over cellular activity via the use of cell-targeting phototransducers, is widely used nowadays to study and modulate/restore biological functions. This approach relies on non-covalent interactions between the phototransducer and the cell membrane, thus implying that cell conditions and membrane status can dictate the effectiveness of the method. For instance, although immortalized cell lines are traditionally used in photostimulation experiments, it has been demonstrated that the number of passages they undergo is correlated to the worsening of cell conditions. In principle, this could impact cell responsivity against exogenous stressors, including photostimulation. However, these aspects have usually been neglected in previous experiments. In this work, we investigated whether cell passages could affect membrane properties (such as polarity and fluidity). We applied optical spectroscopy and electrophysiological measurements in two different biological models: (i) an epithelial immortalized cell line (HEK-293T cells) and (ii) liposomes. Different numbers of cell passages were compared to a different morphology in the liposome membrane. We demonstrated that cell membranes show a significant decrease in ordered domains upon increasing the passage number. Furthermore, we observed that cell responsivity against external stressors is markedly different between aged and non-aged cells. Firstly, we noted that the thermal-disordering effect that is usually observed in membranes is more evident in aged cells than in non-aged ones. We then set up a photostimulation experiment by using a membrane-targeted azobenzene as a phototransducer (Ziapin2). As an example of a functional consequence of such a condition, we showed that the rate of isomerization of an intramembrane molecular transducer is significantly impaired in aged cells. The reduction in the photoisomerization rate translates in cells with a sustained reduction of the Ziapin2-related hyperpolarization of the membrane potential and an overall increase in the molecule fluorescence. Overall, our results suggest that membrane stimulation strongly depends on membrane order, highlighting the importance of cell passage during the characterization of the stimulation tools. This study can shine light on the correlation between aging and the development of diseases driven by membrane degradation as well as on the different cell responsivities against external stressors, such as temperature and photostimulation.

Time perception and pain: Can a temporal illusion reduce the intensity of pain?

It is commonly known-and previous studies have indicated-that time appears to last longer during unpleasant situations. This study examined whether a reciprocal statement can be made-that is, whether changes in the perception of time can influence our judgment (or rating) of a negative event. We used a temporal illusion method (Pomares et al. Pain 152, 230-234, 2011) to induce distortions in the perception of time. Two stimuli were presented for a constant time: a full clock, which stayed on the screen until its clock hand completed a full rotation (360°); and a short clock, in which the clock hand moved just three-quarters of the way (270°), thus suggesting a reduced interval duration. However, both stimuli were shown for the same amount of time. We specifically investigated (a) whether we could induce a temporal illusion with this simple visual manipulation, and (b) whether this illusion could change participants' ratings of a painful stimulus. In Experiment I (n = 22), to answer (a) above, participants were asked to reproduce the duration in which the different clocks were presented. In Experiment II (n = 30), a painful thermal stimulation was applied on participants' hands while the clocks were shown. Participants were asked to rate the perceived intensity of their pain, and to reproduce its duration. Results showed that, for both experiments, participants reproduced a longer interval after watching the full clock compared with the short clock, confirming that the clock manipulation was able to induce a temporal illusion. Furthermore, the second experiment showed that participants rated the thermal stimuli as less painful when delivered with the short clock than with the full clock. These findings suggest that temporal distortions can modulate the experience of pain.

High-speed heating of the skin using a contact thermode elicits brain responses comparable to CO2 laser-evoked potentials.

OBJECTIVE: To compare nociceptive event-related brain potentials elicited by a high-speed contact-thermode vs an infrared CO2 laser stimulator. METHODS: Contact heat-evoked potentials (CHEPs) and CO2 laser-evoked potentials (LEPs) were recorded in healthy volunteers using a high-speed contact-thermode (>200 °C/s) and a temperature-controlled CO2 laser. In separate experiments, stimuli were matched in terms of target surface temperature (55 °C) and intensity of perception. A finite-element model of skin heat transfer was used to explain observed differences. RESULTS: For 55 °C stimuli, CHEPs were reduced in amplitude and delayed in latency as compared to LEPs. For perceptually matched stimuli (CHEPs: 62 °C; LEPs: 55 °C), amplitudes were similar, but CHEPs latencies remained delayed. These differences could be explained by skin thermal inertia producing differences in the heating profile of contact vs radiant heat at the dermo-epidermal junction. CONCLUSIONS: Provided that steep heating ramps are used, and that target temperature is matched at the dermo-epidermal junction, contact and radiant laser heat stimulation elicit responses of similar magnitude. CHEPs are delayed compared to LEPs. SIGNIFICANCE: CHEPs could be used as an alternative to LEPs for the diagnosis of neuropathic pain. Dedicated normative values must be used to account for differences in skin thermal transfer.

SP600125 Enhances Temperature-Controlled Repeated Thermal Stimulation-Induced Neurite Outgrowth in PC12-P1F1 Cells.

This study evaluated the mechanism of temperature-controlled repeated thermal stimulation (TRTS)-mediated neuronal differentiation. We assessed the effect of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, on neuronal differentiation of rat PC12-P1F1 cells, which can differentiate into neuron-like cells by exposure to TRTS or neurotrophic factors, including bone morphogenetic protein (BMP) 4. We evaluated neuritogenesis by incubating the cells under conditions of TRTS and/or SP600125. Cotreatment with SP600125 significantly enhanced TRTS-mediated neuritogenesis, whereas that with other selective mitogen-activated protein kinase (MAPK) inhibitors did not-e.g., extracellular signal-regulated kinase (ERK)1/2 inhibitor U0126, and p38 MAPK inhibitor SB203580. We tried to clarify the mechanism of SP600125 action by testing the effect of U0126 and the BMP receptor inhibitor LDN193189 on the SP600125-mediated enhancement of intracellular signaling. SP600125-enhanced TRTS-induced neuritogenesis was significantly inhibited by U0126 or LDN193189. Gene expression analysis revealed that TRTS significantly increased ß3-Tubulin, MKK3, and Smad7 gene expressions. Additionally, Smad6 and Smad7 gene expressions were substantially attenuated through SP600125 co-treatment during TRTS. Therefore, SP600125 may partly enhance TRTS-induced neuritogenesis by attenuating the negative feedback loop of BMP signaling. Further investigation of the mechanisms underlying the effect of SP600125 during TRTS-mediated neuritogenesis may contribute to the future development of regenerative neuromedicine.

Clinicopathological digital image analyses before and after thermal stimulation subdivide acquired idiopathic generalized anhidrosis into inflammatory and non-inflammatory type.

BACKGROUND: Acquired idiopathic generalized anhidrosis (AIGA) manifests varying degrees of syringotropic inflammation. OBJECTIVE: To better understand the basis of inflammation in AIGA. METHODS: Changes in the extent of cell infiltration around the sweat gland/duct and the difference in the expression level of immune privilege (IP)-related/sweat gland markers before and after thermal stimulation were assessed in AIGA. We also adopted a semi-quantitative digital image analysis of sweating as detected by the starch-iodine method. The changes in sweating before and after treatment was defined as the improvement index. RESULTS: Nine AIGA cases were analyzed. Two cases with minimal inflammation were defined as non-inflammatory type (non-inf)AIGA, while others with evident cell infiltration were defined as inflammatory type (inf)AIGA. MHC class I was significantly upregulated with downregulation of macrophage migration inhibitory factor and alpha-melanocyte-stimulating hormone exclusively in the sweat duct of infAIGA after thermal stimulation (p < 0.05). Furthermore, the extent of inflammation and the ductal dermcidin expression prior to thermal stimulation were inversely correlated (r = - 0.807), while that and the ductal claudin-1 expression after thermal stimulation was positively correlated (r = 0.875). The improvement index positively correlated with the degree of inflammation after thermal stimulation implying possible contribution of inflammation in AIGA pathophysiology. In addition, interferon-induced protein 10 and claudin-1 expression level in the sweat duct before thermal stimulation respectively correlated with the improvement index (r = 0.750, and 0.762). CONCLUSION: The pathophysiology of AIGA may be subcategorized into two groups: IP-collapse possibly play some roles in infAIGA, while ductal dysfunction may exist in non-infAIGA.

Mild thermal stimulation of the buttock skin increases urinary voiding efficiency in anesthetized rats.

In the present study, we examined the effects of mild thermal stimulation of the skin on voiding efficiency using urethane-anesthetized rats with reduced voiding efficiency. Spontaneous urination was induced by infusing saline. For each voiding, the voiding efficiency was calculated from the voided volume and the bladder capacity measured. A Peltier thermode was attached to the buttock skin to apply stimulation: cooling between to 25 °C and 35 °C, every 20 s throughout the saline infusion. The voiding efficiency was 29 ± 9 % (mean ± SD) before stimulation and increased significantly by 10-15 % during stimulation. During thermal stimulation, the maximum vesical pressure during micturition was unchanged, but the urethral relaxation duration was significantly prolonged. Applying local anesthesia to the stimulated skin area abolished the changes in voiding efficiency in response to thermal stimulation. These results suggest that the excitation of cutaneous thermoreceptive afferents modulates urethral function during urination, thereby improving voiding efficiency.

Prussian Blue Nanoparticle-Mediated Scalable Thermal Stimulation for In Vitro Neuronal Differentiation.

Heating has recently been applied as an alternative to electrical stimulation to modulate excitability and to induce neuritogenesis and the expression of neuronal markers; however, a long-term functional differentiation has not been described so far. Here, we present the results obtained by a new approach for scalable thermal stimulation on the behavior of a model of dorsal root ganglion neurons, the F-11 cell line. Initially, we performed experiments of bulk stimulation in an incubator for different time intervals and temperatures, and significant differences in neurite elongation and in electrophysiological properties were observed in cultures exposed at 41.5 °C for 30 min. Thus, we exposed the cultures to the same temperature increase using a near-infrared laser to irradiate a disc of Prussian blue nanoparticles and poly-vinyl alcohol that we had adhered to the outer surface of the petri dish. In irradiated cells, neurites were significantly longer, and the electrophysiological properties (action potential firing frequency and spontaneous activity) were significantly increased compared to the control. These results show for the first time that a targeted thermal stimulation could induce morphological and functional neuronal differentiation and support the future application of this method as a strategy to modify neuronal behavior in vivo.

Novel temperature-controlled sleep system to improve sleep: a proof-of-concept study.

The sleep-wake cycle is regulated by circadian Process C and homeostatic Process S. Selective thermal stimulation (STS) of the cervical spine region enhances glabrous skin blood flow (GSBF) and augments body heat dissipation to increase distal-to-proximal skin gradient (DPG) causing decrease of core body temperature (CBT), which can shorten sleep onset latency (SOL) and improve sleep quality. A total of 11 young healthy/normal sleeper males challenged to go to bed (lights-off) 2 h earlier than usual were subjected in a randomised order to non-consecutive treatment and control night-time sleep sessions. The treatment night entailed activation of a dual-temperature zone mattress with a cooler centre and warmer periphery plus STS pillow that applied mild heating to the cervical spinal skin for 30 min after lights-off for sleep. During the first 30 min after lights-off, GSBF (mean [standard error (SE)] Δ = 49.77 [19.13] perfusion units, p = 0.013) and DPG (mean [SE] Δ = 2.05 [0.62] °C, p = 0.005) were significantly higher and CBT (mean [SE] Δ = -0.15 [0.07] °C, p = 0.029) was significantly lower in the treatment than control night, while there was no significant difference in these variables during the 45 min prior to lights-off (baseline). Moreover, SOL was significantly reduced (mean [SE] Δ = -48.6 [23.4] min, p = 0.032) and subjective sleep quality significantly better (p < 0.001) in the treatment than control night. In conclusion, the novel sleep facilitating system comprised of the STS pillow plus dual-temperature zone mattress induced earlier increase in GSBF and DPG and earlier decline in CBT. This resulted in statistically significant shortened SOL and improved overall sleep quality, thereby reducing sleep pressure of Process S, even under the challenging investigative protocol requiring participants to go to sleep 2 h earlier than customary.

Mahuang Xixin Fuzi decoction ameliorates apoptosis via the mitochondrial-mediated signaling pathway in MCM cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Mahuang Xixin Fuzi Decoction (MXF), as a classical prescription of traditional Chinese medicine (TCM), has been used to treat the symptoms of fever, nasal congestion and headache in elderly people for almost a thousand years. AIM OF THE STUDY: The purpose of this study was to evaluate the effects and possible mechanisms of MXF on thermal stimulation-induced mouse cardiac myocytes (MCM) cell apoptosis. MATERIALS AND METHODS: The apoptosis of the MCM cell model was induced by a PCR-calculated temperature control system with a gradual heating pattern at 43 °C for 1 h. The cytotoxic effects were determined using real-time cell analyzer (RTCA) technology. Annexin V-FITC/7-AAD staining, and JC-1 fluorescence were used to assess apoptosis. Specific substrates, enzyme-linked immunosorbent assays (ELISAs), and Western blotting were used to identify proteins in the mitochondrial-mediated pathway. The identification of chemical components in the mouse heart was performed by ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry analysis. RESULTS: MXF inhibited apoptosis through the mitochondrial-mediated signaling pathway, including ameliorating ∆Ψm reduction, blocking mitochondrial Cyt C release, reducing Bax levels and increasing Bcl-2 levels, suppressing caspase-9 and caspase-3 activation in cytoplasmic fractions. Moreover, the components of MXF that act on the heart are mainly ephedra alkaloids and aconitine alkaloids. CONCLUSIONS: The findings demonstrated that MXF treatment markedly reduced MCM cell apoptosis induced by thermal stimulation, which may be ascribed to the mitochondrial-mediated signaling pathway.

Emerging approaches of neural regeneration using physical stimulations solely or coupled with smart piezoelectric nano-biomaterials.

Neural regeneration is a challenging venture as it is limited by various intrinsic physiological parameters such as the presence of biomolecules like Nogo-A, Ephrin-B3 and Neurocan, that inhibit Central nervous system (CNS) regeneration, and the absence of conducive factors such as ATF3, Sox2 and GAP-43, that promote the neuronal differentiation and regeneration. The design of an effective strategy for neuronal repair or regeneration is a daunting task as neural cells are responsive to a very narrow window of the conductive cellular microenvironment. It requires specific inductive signals and chemical cues from neighbouring cells that can trigger the process of regeneration or repair. It is this complexity that adds to the plight in the scenarios of patients confronted with trauma resulting in spinal cord injury (SCI) or traumatic brain injury (TBI). SCI or TBI may cause temporary or permanent locomotory disorders in patients, affecting the quality of their lives. The regenerative potential of neural cells in the CNS is comparatively lesser than that of peripheral nervous system (PNS). Also, the activation and migration of astrocytes to the injury site causes glial scar, thus hindering further repair process, especially in CNS injuries. Therefore, an effective strategy for stimulating neuritic branching and growth can be a solution to the problem. This review discusses the various facets of strategies that have been adopted to understand and improve the progress of neural tissue engineering for treating the conditions like SCI and TBI. This review also provides an insight regarding the influence of various nano-topographical cues on neuronal cell behavior, the importance of inherent piezoelectric properties in biological systems, various forms of physical stimulation methods that can drive the process of neuritic outgrowth, and finally concludes with the elucidations of advances in development of various biomaterials that have been found effective in achieving enhancement in neuronal physiological properties. It also shares some opinions as perspectives that may help in the further advancement of this field.

A case of Raynaud's phenomenon of toes induced by whole-body warm stimulation.

Raynaud's phenomenon, induced by cold stimulation and emotional stress, is also induced by whole-body warm stimulation. A 74-year-old man was referred to our department because of nocturnal toe pain from 2 years prior and immediate color change of the toes from 1 year prior when submerging himself into a warm bath. Physical examination and blood tests revealed no abnormal findings suggestive of secondary Raynaud's phenomenon. Two years later, the signs and symptoms persisted. When physicians confirm Reynaud's phenomenon, they should check for the possibility of secondary Reynaud's phenomenon. Additional research on Reynaud's phenomenon induced by warm stimulation is needed.

Selective retina therapy and thermal stimulation of the retina: different regenerative properties - implications for AMD therapy.

BACKGROUND: Selective Retina Therapy (SRT), a photodisruptive micropulsed laser modality that selectively destroys RPE cells followed by regeneration, and Thermal Stimulation of the Retina (TSR), a stimulative photothermal continuous wave laser modality that leads to an instant sublethal temperature increase in RPE cells, have shown therapeutic effects on Age-related Macular Degeneration (AMD) in mice. We investigate the differences between both laser modalities concerning RPE regeneration. METHODS: For PCR array, 6 eyes of murine AMD models, apolipoprotein E and nuclear factor erythroid-derived 2- like 2 knock out mice respectively, were treated by neuroretina-sparing TSR or SRT. Untreated litter mates were controls. Eyes were enucleated either 1 or 7 days after laser treatment. For morphological analysis, porcine RPE/choroid organ cultures underwent the same laser treatment and were examined by calcein vitality staining 1 h and 1, 3 or 5 days after irradiation. RESULTS: TSR did not induce the expression of cell-mediators connected to cell death. SRT induced necrosis associated cytokines as well as inflammation 1 but not 7 days after treatment. Morphologically, 1 h after TSR, there was no cell damage. One and 3 days after TSR, dense chromatin and cell destruction of single cells was seen. Five days after TSR, there were signs of migration and proliferation. In contrast, 1 h after SRT a defined necrotic area within the laser spot was seen. This lesion was closed over days by migration and proliferation of adjacent cells. CONCLUSIONS: SRT induces RPE cell death, followed by regeneration within a few days. It is accompanied by necrosis induced inflammation, RPE proliferation and migration. TSR does not induce immediate RPE cell death; however, migration and mitosis can be seen a few days after laser irradiation, not accompanied by necrosis-associated inflammation. Both might be a therapeutic option for the treatment of AMD.

Determination of the temperature causing a nociceptive response in the tail of albino BALB/c mice.

INTRODUCTION: Designs for determining nociceptive response in rodents are of great use in neurology and experimental neuroscience. Immersing mice's tails in warm water is one of the most widely used procedures to evaluate this response; however, a wide range of temperatures are used in different studies. Knowing the temperature that produces a powerful nociceptive response in the tail of BALB/c mice is extremely useful. METHODS: Eight 2-month-old male BALB/c mice were used. A 14-cm high beaker was filled with water up to 13cm. The animals' tails were immersed in the container with a starting temperature of 36°C. The water temperature was raised in 1°C increments until we identified the temperatures that produced nociceptive responses. That response was determined by counting the time taken before the mouse shook its tail to remove it from the water. RESULTS: Six of the 8 mice began shaking their tails at the temperature of 51°C. All animals removed their tails from the water at the temperatures of 54°C, 55°C, and 56°C, taking a mean time of 8.54, 7.99, and 5.33seconds, respectively. ANOVA applied to the response times for each of the 3 temperatures indicated revealed a value of F=2.8 (P=.123). CONCLUSIONS: The response time was statistically similar for the temperatures of 54°C, 55°C, and 56°C; however, the data were less dispersed for the latter temperature.

Determinación de la temperatura de respuesta nociceptiva sobre la cola de ratones albinos de la cepa Balb/c / Determination of the temperature causing a nociceptive response in the tail of albino BALB/c mice

Introducción: Los diseños para determinar la respuesta nociceptiva en roedores son de gran utilidad en neurología y en neurociencias experimentales. El paradigma de inmersión de la cola de ratón en agua temperada es uno de los más empleados para evaluar dicha respuesta; sin embargo, existe amplia variación en la temperatura utilizada en las diversas investigaciones. Resulta sumamente útil determinar la temperatura que produce una mejor respuesta nociceptiva sobre la cola de ratones de la cepa Balb/c.MétodosSe emplearon 8 ratones machos Balb/c de 2 meses de edad. Un beaker de 14 cm de alto se llenó de agua hasta 13 cm. Partiendo desde los 36 °C se empezó a sumergir la cola del animal dentro del recipiente. Se comenzó a elevar en 1 °C el agua hasta encontrar las temperaturas que produzcan las respuestas nociceptivas. Dicha respuesta se determinó contabilizando el tiempo que el ratón tardó en sacudir su cola retirándola del agua.ResultadosLos ratones empezaron a sacudir su cola a los 51 °C (6 de los 8 roedores). El total de la muestra retiró su cola del agua a los 54, 55 y 56 °C en el tiempo promedio de 8,54, 7,99 y 5,33 s, respectivamente. Al aplicar ANOVA a los tiempos de las 3 temperaturas señaladas se obtuvo el valor F = 2,8 y p = 0,123.ConclusionesEl tiempo de respuesta fue similar estadísticamente ante las temperaturas de 54, 55 y 56 °C; sin embargo se encontró menor dispersión de los datos ante esta última. (AU)

Introduction: Designs for determining nociceptive response in rodents are of great use in neurology and experimental neuroscience. Immersing mice's tails in warm water is one of the most widely used procedures to evaluate this response; however, a wide range of temperatures are used in different studies. Knowing the temperature that produces a powerful nociceptive response in the tail of BALB/c mice is extremely useful.MethodsEight 2-month-old male BALB/c mice were used. A 14-cm high beaker was filled with water up to 13 cm. The animals’ tails were immersed in the container with a starting temperature of 36 °C. The water temperature was raised in 1 °C increments until we identified the temperatures that produced nociceptive responses. That response was determined by counting the time taken before the mouse shook its tail to remove it from the water.ResultsSix of the 8 mice began shaking their tails at the temperature of 51 °C. All animals removed their tails from the water at the temperatures of 54 °C, 55 °C, and 56 °C, taking a mean time of 8.54, 7.99, and 5.33 seconds, respectively. ANOVA applied to the response times for each of the 3 temperatures indicated revealed a value of F=2.8 (P=.123).ConclusionsThe response time was statistically similar for the temperatures of 54 °C, 55 °C, and 56 °C; however, the data were less dispersed for the latter temperature. (AU)

Numerical Investigation into the Gas Production from Hydrate Deposit under Various Thermal Stimulation Modes in a Multi-Well System in Qilian Mountain.

The primary objective of this study was to investigate the energy recovery performance of the permafrost hydrate deposit in the Qilian Mountain at site DK-2 using depressurization combined with thermal injection by the approach of numerical simulation. A novel multi-well system with five horizontal wells was applied for large-scale hydrate mining. The external heat is provided by means of water injection, wellbore heating, or the combinations of them through the central horizontal well, while the fluids are extracted outside from the other four production wells under constant depressurization conditions. The injected water can carry the heat into the hydrate deposit with a faster rate by thermal convection regime, while it also raises the local pressure obviously, which results in a strong prohibition effect on hydrate decomposition in the region close to the central well. The water production rate is always controllable when using the multi-well system. No gas seepage is observed in the reservoir due to the resistance of the undissociated hydrate. Compared with hot water injection, the electric heating combined with normal temperature water flooding basically shows the same promotion effect on gas recovery. Although the hydrate regeneration is more severe in the case of pure electric heating, the external heat can be more efficiently assimilated by gas hydrate, and the efficiency of gas production is best compared with the cases involving water injection. Thus, pure wellbore heating without water injection would be more suitable for hydrate development in deposits characterized by low-permeability conditions.

Response of Retinal Pigment Epithelium (RPE)-Choroid Explants to Thermal Stimulation Therapy of the RPE (TSR).

BACKGROUND AND OBJECTIVES: The thermal stimulation therapy of the retinal pigment epithelium (TSR) is a sublethal laser technique for thermal stimulation of the retinal pigment epithelium (RPE)-Bruch's membrane (BrM)-complex. The aim of this study was to investigate the influence of TSR on the release of age-related macular degeneration (AMD)-relevant cell mediators. STUDY DESIGN/MATERIALS AND METHODS: Porcine RPE-BrM-choroid explants were irradiated with a 532 nm continuous wave laser using different spot sizes (100-300 µm, duration 100 milliseconds, 15-100 mW). Cell death was investigated by calcein staining. Explants were treated with grids of sublethal spots and cultivated in modified Ussing chambers. The effect on matrix metalloproteinase-2 (MMP-2) and -9 was investigated by zymography and quantitative reverse transcription polymerase chain reaction. Secretion of vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF), and transforming growth factor-ß (TGF-ß) was analyzed by enzyme-linked immunosorbent assay and expression of HSP70 was examined by western blot. Integrity of the RPE/BrM-complex was analyzed by scanning electron microscopy. RESULTS: Laser powers of 15 mW (100 µm) and 45 mW (300 µm) did not induce RPE cell death. The integrity of the RPE/BrM-complex was not impaired after TSR. After TSR with 300 µm spot size, we observed a significant increase of active MMP-2 in the basal compartments. The content of PEDF significantly increased in treated explants in both compartments with 100 and 300 µm spot sizes. VEGF and TGF-ß secretion was not triggered by TSR. CONCLUSIONS: TSR represents a possible RPE stimulating treatment for dry AMD. TSR increases the basal release of active MMP-2, which might reverse age-related thickening of BrM. VEGF secretion was not triggered by TSR while anti-angiogenic PEDF was increased, indicating an induction of an anti-angiogenic and neuroprotective environment. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Alternate thermal stimulation ameliorates thermal sensitivity and modulates calbindin-D 28K expression in lamina I and II and dorsal root ganglia in a mouse spinal cord contusion injury model.

Neuropathic pain (NP) is a common complication that negatively affects the lives of patients with spinal cord injury (SCI). The disruption in the balance of excitatory and inhibitory neurons in the spinal cord dorsal horn contributes to the development of SCI and induces NP. The calcium-binding protein (CaBP) calbindin-D 28K (CaBP-28K) is highly expressed in excitatory interneurons, and the CaBP parvalbumin (PV) is present in inhibitory neurons in the dorsal horn. To better define the changes in the CaBPs contributing to the development of SCI-induced NP, we examined the changes in CaBP-28K and PV staining density in the lumbar (L4-6) lamina I and II, and their relationship with NP after mild spinal cord contusion injury in mice. We additionally examined the effects of alternate thermal stimulation (ATS). Compared with sham mice, injured animals developed mechanical allodynia in response to light mechanical stimuli and exhibited mechanical hyporesponsiveness to noxious mechanical stimuli. The decreased response latency to heat stimuli and increased response latency to cold stimuli at 7 days post injury suggested that the injured mice developed heat hyperalgesia and cold hypoalgesia, respectively. Temperature preference tests showed significant warm allodynia after injury. Animals that underwent ATS (15-18 and 35-40°C; +5 minutes/stimulation/day; 5 days/week) displayed significant amelioration of heat hyperalgesia, cold hypoalgesia, and warm allodynia after 2 weeks of ATS. In contrast, mechanical sensitivity was not influenced by ATS. Analysis of the CaBP-28K positive signal in L4-6 lamina I and II indicated an increase in staining density after SCI, which was associated with an increase in the number of CaBP-28K-stained L4-6 dorsal root ganglion (DRG) neurons. ATS decreased the CaBP-28K staining density in L4-6 spinal cord and DRG in injured animals, and was significantly and strongly correlated with ATS alleviation of pain behavior. The expression of PV showed no changes in lamina I and II after ATS in SCI animals. Thus, ATS partially decreases the pain behavior after SCI by modulating the changes in CaBP-associated excitatory-inhibitory neurons.