Interdependency of Core Temperature and Glabrous Skin Blood Flow in Human Thermoregulation Function: A Pilot Study.

Human thermoregulation is governed by a complex, nonlinear feedback control system. The system consists of thermoreceptors, a controller, and effector mechanisms for heat exchange that coordinate to maintain a central core temperature. A principal route for heat flow between the core and the environment is via convective circulation of blood to arteriovenous anastomoses located in glabrous skin of the hands and feet. This paper presents new human experimental data for thermoregulatory control behavior along with a coupled, detailed control system model specific to the interdependent actions of core temperature and glabrous skin blood flow (GSBF) under defined transient environmental thermal stress. The model was tuned by a nonlinear least-squared curve fitting algorithm to optimally fit the experimental data. Transient GSBF in the model is influenced by core temperature, nonglabrous skin temperature, and the application of selective thermal stimulation. The core temperature in the model is influenced by integrated heat transfer across the nonglabrous body surface and GSBF. Thus, there is a strong cross-coupling between GSBF and core temperature in thermoregulatory function. Both variables include a projection term in the model based on the average rates of their change. Six subjects each completed two thermal protocols to generate data to which the common model was fit. The model coefficients were unique to each of the twelve data sets but produced an excellent agreement between the model and experimental data for the individual trials. The strong match between the model and data confirms the mathematical structure of the control algorithm.

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.

Bioheat Transfer Basis of Human Thermoregulation: Principles and Applications.

Thermoregulation is a process that is essential to the maintenance of life for all warm-blooded mammalian and avian species. It sustains a constant core body temperature in the face of a wide array of environmental thermal conditions and intensity of physical activities that generate internal heat. A primary component of thermoregulatory function is the movement of heat between the body core and the surface via the circulation of blood. The peripheral vasculature acts as a forced convection heat exchanger between blood and local peripheral tissues throughout the body enabling heat to be convected to the skin surface where is may be transferred to and from the environment via conduction, convection, radiation, and/or evaporation of water as local conditions dictate. Humans have evolved a particular vascular structure in glabrous (hairless) skin that is especially well suited for heat exchange. These vessels are called arteriovenous anastomoses (AVAs) and can vasodilate to large diameters and accommodate high flow rates. We report herein a new technology based on a physiological principle that enables simple and safe access to the thermoregulatory control system to allow manipulation of thermoregulatory function. The technology operates by applying a small amount of heating local to control tissue on the body surface overlying the cerebral spine that upregulates AVA perfusion. Under this action, heat exchangers can be applied to glabrous skin, preferably on the palms and soles, to alter the temperature of elevated blood flow prior to its return to the core. Therapeutic and prophylactic applications are discussed.

Insights and Experiences in Academic Mentoring and Education.

It is a great honor to be named the awardee of the 2019 ASME Robert M. Nerem Education and Mentorship Medal. Bob Nerem has been a mentor to me since the beginning of my faculty career and has been a model to me for effectively dealing with the many dimensions of the interpersonal side of an academic career. This brief paper presents a summary of some of my personal insights and practices in this arena as gained during 46 years on the faculty of the University of Texas at Austin.

Deep Neural Network Sleep Scoring Using Combined Motion and Heart Rate Variability Data.

Background: Performance of wrist actigraphy in assessing sleep not only depends on the sensor technology of the actigraph hardware but also on the attributes of the interpretative algorithm (IA). The objective of our research was to improve assessment of sleep quality, relative to existing IAs, through development of a novel IA using deep learning methods, utilizing as input activity count and heart rate variability (HRV) metrics of different window length (number of epochs of data). Methods: Simultaneously recorded polysomnography (PSG) and wrist actigraphy data of 222 participants were utilized. Classic deep learning models were applied to: (a) activity count alone (without HRV), (b) activity count + HRV (30-s window), (c) activity count + HRV (3-min window), and (d) activity count + HRV (5-min window) to ascertain the best set of inputs. A novel deep learning model (Haghayegh Algorithm, HA), founded on best set of inputs, was developed, and its sleep scoring performance was then compared with the most popular University of California San Diego (UCSD) and Actiwatch proprietary IAs. Results: Activity count combined with HRV metrics calculated per 5-min window produced highest agreement with PSG. HA showed 84.5% accuracy (5.3-6.2% higher than comparator IAs), 89.5% sensitivity (6.2% higher than UCSD IA and 6% lower than Actiwatch proprietary IA), 70.0% specificity (8.2-34.3% higher than comparator IAs), and 58.7% Kappa agreement (16-23% higher than comparator IAs) in detecting sleep epochs. HA did not differ significantly from PSG in deriving sleep parameters-sleep efficiency, total sleep time, sleep onset latency, and wake after sleep onset; moreover, bias and mean absolute error of the HA model in estimating them was less than the comparator IAs. HA showed, respectively, 40.9% and 54.0% Kappa agreement with PSG in detecting rapid and non-rapid eye movement (REM and NREM) epochs. Conclusions: The HA model simultaneously incorporating activity count and HRV metrics calculated per 5-min window demonstrates significantly better sleep scoring performance than existing popular IAs.

From Nanowarming to Thermoregulation: New Multiscale Applications of Bioheat Transfer.

This review explores bioheat transfer applications at multiple scales from nanoparticle (NP) heating to whole-body thermoregulation. For instance, iron oxide nanoparticles are being used for nanowarming, which uniformly and quickly rewarms 50-80-mL (≤5-cm-diameter) vitrified systems by coupling with radio-frequency (RF) fields where standard convective warming fails. A modification of this approach can also be used to successfully rewarm cryopreserved fish embryos (∼0.8 mm diameter) by heating previously injected gold nanoparticles with millisecond pulsed laser irradiation where standard convective warming fails. Finally, laser-induced heating of gold nanoparticles can improve the sensitivity of lateral flow assays (LFAs) so that they are competitive with laboratory tests such as the enzyme-linked immunosorbent assay. This approach addresses the main weakness of LFAs, which are otherwise the cheapest, easiest, and fastest to use point-of-care diagnostic tests in the world. Body core temperature manipulation has now become possible through selective thermal stimulation (STS) approaches. For instance, simple and safe heating of selected areas of the skin surface can open arteriovenous anastomosis flow in glabrous skin when it is not already established, thereby creating a convenient and effective pathway to induce heat flow between the body core and environment. This has led to new applications of STS to increase or decrease core temperatures in humans and animals to assist in surgery (perioperative warming), to aid ischemic stress recovery (cooling), and even to enhance the quality of sleep. Together, these multiscale applications of nanoparticle heating and thermoregulation point to dramatic opportunities for translation and impact in these prophylactic, preservative, diagnostic, and therapeutic applications of bioheat transfer.

Selective Thermal Stimulation Delays the Progression of Vasoconstriction During Body Cooling.

The objective of this study was to test the feasibility of selective thermal stimulation (STS) as a method to upregulate glabrous skin blood flow. STS is accomplished by mild surface heating along the spinal cord. Four healthy subjects were tested in this study. Each participated in a control experiment and an intervention experiment (STS). Both experiments included establishing a maximum level of vasodilation, considered unique to a subject on a test day, and then cooling to a maximum level of vasoconstriction. Perfusion was measured by a laser Doppler flow probe on the index fingertip. The percent of perfusion in the range of minimum to maximum was the primary outcome variable. The data were fit to a linear mixed effects model to determine if STS had a significant influence on perfusion during whole body cooling. STS had a statistically significant effect on perfusion and increased glabrous skin blood flow by 16.3% (P < 0.001, CI (13.1%, 19.5%)) as skin temperature was decreased. This study supports the theory that STS improves the heat exchanger efficiency of palmar and plantar surfaces by increasing the blood flow.

Accuracy of Wristband Fitbit Models in Assessing Sleep: Systematic Review and Meta-Analysis.

BACKGROUND: Wearable sleep monitors are of high interest to consumers and researchers because of their ability to provide estimation of sleep patterns in free-living conditions in a cost-efficient way. OBJECTIVE: We conducted a systematic review of publications reporting on the performance of wristband Fitbit models in assessing sleep parameters and stages. METHODS: In adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we comprehensively searched the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Embase, MEDLINE, PubMed, PsycINFO, and Web of Science databases using the keyword Fitbit to identify relevant publications meeting predefined inclusion and exclusion criteria. RESULTS: The search yielded 3085 candidate articles. After eliminating duplicates and in compliance with inclusion and exclusion criteria, 22 articles qualified for systematic review, with 8 providing quantitative data for meta-analysis. In reference to polysomnography (PSG), nonsleep-staging Fitbit models tended to overestimate total sleep time (TST; range from approximately 7 to 67 mins; effect size=-0.51, P<.001; heterogenicity: I2=8.8%, P=.36) and sleep efficiency (SE; range from approximately 2% to 15%; effect size=-0.74, P<.001; heterogenicity: I2=24.0%, P=.25), and underestimate wake after sleep onset (WASO; range from approximately 6 to 44 mins; effect size=0.60, P<.001; heterogenicity: I2=0%, P=.92) and there was no significant difference in sleep onset latency (SOL; P=.37; heterogenicity: I2=0%, P=.92). In reference to PSG, nonsleep-staging Fitbit models correctly identified sleep epochs with accuracy values between 0.81 and 0.91, sensitivity values between 0.87 and 0.99, and specificity values between 0.10 and 0.52. Recent-generation Fitbit models that collectively utilize heart rate variability and body movement to assess sleep stages performed better than early-generation nonsleep-staging ones that utilize only body movement. Sleep-staging Fitbit models, in comparison to PSG, showed no significant difference in measured values of WASO (P=.25; heterogenicity: I2=0%, P=.92), TST (P=.29; heterogenicity: I2=0%, P=.98), and SE (P=.19) but they underestimated SOL (P=.03; heterogenicity: I2=0%, P=.66). Sleep-staging Fitbit models showed higher sensitivity (0.95-0.96) and specificity (0.58-0.69) values in detecting sleep epochs than nonsleep-staging models and those reported in the literature for regular wrist actigraphy. CONCLUSIONS: Sleep-staging Fitbit models showed promising performance, especially in differentiating wake from sleep. However, although these models are a convenient and economical means for consumers to obtain gross estimates of sleep parameters and time spent in sleep stages, they are of limited specificity and are not a substitute for PSG.

Pronounced and sustained cutaneous vasoconstriction during and following cyrotherapy treatment: Role of neurotransmitters released from sympathetic nerves.

Cryotherapy is a therapeutic technique using ice or cold water applied to the skin to manage soft tissue trauma and injury. While beneficial, there are some potentially detrimental side effects, such as pronounced vasoconstriction and tissue ischemia that are sustained for hours post-treatment. This study tested the hypothesis that this vasoconstriction is mediated by 1) activation of post-synaptic α-adrenergic receptors and/or 2) activation of post-synaptic neuropeptide Y1 (NPY Y1) receptors. 8 subjects were fitted with a commercially available cryotherapy unit with a water perfused bladder on the lateral portion of the right calf. Participants were instrumented with four intradermal microdialysis probes beneath the bladder. The following conditions were applied at the four treatment sites: 1) control (Ringer solution), 2) combined post-synaptic ß-adrenergic receptors and neuropeptide (NPY) Y1 receptors blockade (P+B site), 3) combined post-synaptic α-adrenergic receptor, ß-adrenergic receptor, and NPY Y1 receptor blockade (Y+P+B site), and 4) blockade of pre-synaptic release of all neurotransmitters from the sympathetic nerves (BT site). Following thermoneutral baseline data collection, 1°C water was perfused through the bladder for 30min, followed by passive rewarming for 60min. Skin temperature (Tskin) fell from ~34°C to ~18.5°C during active cooling across all sites and there was no difference between sites (P>0.05 vs. control for each site). During passive rewarming Tskin rose to a similar degree in all sites (P>0.05 relative to the end of cooling). In the first 20min of cooling %CVC was reduced at all sites however, this response was blunted in the BT and the Y+P+B sites (P>0.05 for all comparisons). By the end of cooling the degree of vasoconstriction was similar between sites with the exception that the reduction in %CVC in the Y+B+P site was less relative to the reduction in the control site. %CVC was unchanged in any of the sites during passive rewarming such that each remained similar to values obtained at the end of active cooling. These findings indicate that the initial vasoconstriction (i.e. within the 1st 20min) that occurs during cryotherapy induced local cooling is achieved via activation of post-synaptic α-adrenergic receptors; whereas nonadrenergic mechanisms predominate as the duration of cooling continues. The sustained vasoconstriction that occurs following cessation of the cooling stimulus does not appear to be related to activation of post-synaptic α-adrenergic receptors or NPY Y1 receptor.

Sustained cutaneous vasoconstriction during and following cyrotherapy treatment: Role of oxidative stress and Rho kinase.

Cryotherapy is a therapeutic technique using ice or cold water applied to the skin to reduce bleeding, inflammation, pain, and swelling following soft tissue trauma and injury. While beneficial, there are some side effects such as pronounced vasoconstriction and tissue ischemia that are sustained for hours post-treatment. This study tested the hypothesis that this vasoconstriction is mediated by 1) the Rho-kinase pathway and/or 2) elevated oxidative stress. 9 subjects were fitted with a commercially available cryotherapy unit with a water perfused bladder on the lateral portion of the right calf. Participants were instrumented with three microdialysis probes underneath the bladder. One site received lactated ringers (control site), one received the Rho-Kinase inhibitor Fasudil, and one received Ascorbic Acid. Skin temperature (Tskin) and cutaneous vascular conductance (CVC) was measured at each site. Subjects had 1°C water perfused through the bladder for 30min, followed by passive rewarming for 90min. Tskin fell from ~34°C to ~18.0°C during active cooling across all sites and this response was similar for all sites (P>0.05 for all comparisons). During passive rewarming Tskin rose to a similar degree in all sites (P>0.05 relative to the end of cooling). %CVC was reduced during active cooling in all sites; however, the magnitude of this response was blunted in the Fasudil site relative to control (P<0.001 for all comparisons) and min 25 and 30 of cooling in the Ascorbic Acid site (P<0.05). During passive rewarming %CVC at the control and Ascorbic Acid sites did not change such that values were similar to the end of cooling (P>0.05 for each comparison). %CVC at the Fasudil site remained elevated during passive rewarming such that values were higher compared to the control and Ascorbic Acid sites throughout the 90min of passive rewarming (P<0.001 main effect of Fasudil). These findings indicate that the Rho-kinase pathway contributes to pronounced vasoconstriction during cryotherapy as well as the sustained vasoconstriction during the subsequent rewarming period post treatment.

Cryotherapy-Induced Persistent Vasoconstriction After Cutaneous Cooling: Hysteresis Between Skin Temperature and Blood Perfusion.

The goal of this study was to investigate the persistence of cold-induced vasoconstriction following cessation of active skin-surface cooling. This study demonstrates a hysteresis effect that develops between skin temperature and blood perfusion during the cooling and subsequent rewarming period. An Arctic Ice cryotherapy unit (CTU) was applied to the knee region of six healthy subjects for 60 min of active cooling followed by 120 min of passive rewarming. Multiple laser Doppler flowmetry perfusion probes were used to measure skin blood flow (expressed as cutaneous vascular conductance (CVC)). Skin surface cooling produced a significant reduction in CVC (P < 0.001) that persisted throughout the duration of the rewarming period. In addition, there was a hysteresis effect between CVC and skin temperature during the cooling and subsequent rewarming cycle (P < 0.01). Mixed model regression (MMR) showed a significant difference in the slopes of the CVC-skin temperature curves during cooling and rewarming (P < 0.001). Piecewise regression was used to investigate the temperature thresholds for acceleration of CVC during the cooling and rewarming periods. The two thresholds were shown to be significantly different (P = 0.003). The results show that localized cooling causes significant vasoconstriction that continues beyond the active cooling period despite skin temperatures returning toward baseline values. The significant and persistent reduction in skin perfusion may contribute to nonfreezing cold injury (NFCI) associated with cryotherapy.

Cold-induced vasoconstriction may persist long after cooling ends: an evaluation of multiple cryotherapy units.

PURPOSE: Localized cooling is widely used in treating soft tissue injuries by modulating swelling, pain, and inflammation. One of the primary outcomes of localized cooling is vasoconstriction within the underlying skin. It is thought that in some instances, cryotherapy may be causative of tissue necrosis and neuropathy via cold-induced ischaemia leading to nonfreezing cold injury (NFCI). The purpose of this study is to quantify the magnitude and persistence of vasoconstriction associated with cryotherapy. METHODS: Data are presented from testing with four different FDA approved cryotherapy devices. Blood perfusion and skin temperature were measured at multiple anatomical sites during baseline, active cooling, and passive rewarming periods. RESULTS: Local cutaneous blood perfusion was depressed in response to cooling the skin surface with all devices, including the DonJoy (DJO, p = 2.6 × 10(-8)), Polar Care 300 (PC300, p = 1.1 × 10(-3)), Polar Care 500 Lite (PC500L, p = 0.010), and DeRoyal T505 (DR505, p = 0.016). During the rewarming period, parasitic heat gain from the underlying tissues and the environment resulted in increased temperatures of the skin and pad for all devices, but blood perfusion did not change significantly, DJO (n.s.), PC300 (n.s.), PC500L (n.s.), and DR505 (n.s.). CONCLUSIONS: The results demonstrate that cryotherapy can create a deep state of vasoconstriction in the local area of treatment. In the absence of independent stimulation, the condition of reduced blood flow persists long after cooling is stopped and local temperatures have rewarmed towards the normal range, indicating that the maintenance of vasoconstriction is not directly dependent on the continuing existence of a cold state. The depressed blood flow may dispose tissue to NFCI.

Heat Transfer in Health and Healing.

Our bodies depend on an exquisitely sensitive and refined temperature control system to maintain a state of health and homeostasis. The exceptionally broad range of physical activities that humans engage in and the diverse array of environmental conditions we face require remarkable strategies and mechanisms for regulating internal and external heat transfer processes. On the occasions for which the body suffers trauma, therapeutic temperature modulation is often the approach of choice for reversing injury and inflammation and launching a cascade of healing. The focus of human thermoregulation is maintenance of the body core temperature within a tight range of values, even as internal rates of energy generation may vary over an order of magnitude, environmental convection, and radiation heat loads may undergo large changes in the absence of any significant personal control, surface insulation may be added or removed, all occurring while the body's internal thermostat follows a diurnal circadian cycle that may be altered by illness and anesthetic agents. An advanced level of understanding of the complex physiological function and control of the human body may be combined with skill in heat transfer analysis and design to develop life-saving and injury-healing medical devices. This paper will describe some of the challenges and conquests the author has experienced related to the practice of heat transfer for maintenance of health and enhancement of healing processes.

Thermally induced apoptosis, necrosis, and heat shock protein expression in 3D culture.

This study was conducted to compare the heat shock responses of cells grown in 2D and 3D culture environments as indicated by the level of heat shock protein 70 expression and the incidence of apoptosis and necrosis of prostate cancer cell lines in response to graded hyperthermia. PC3 cells were stably transduced with a dual reporter system composed of two tandem expression cassettes-a conditional heat shock protein promoter driving the expression of green fluorescent protein (HSPp-GFP) and a cytomegalovirus (CMV) promoter controlling the constitutive expression of a "beacon" red fluorescent protein (CMVp-RFP). Two-dimensional and three-dimensional cultures of PC3 prostate cancer cells were grown in 96-well plates for evaluation of their time-dependent response to supraphysiological temperature. To induce controlled hyperthermia, culture plates were placed on a flat copper surface of a circulating water manifold that maintained the specimens within ±0.1°C of a target temperature. Hyperthermia protocols included various combinations of temperature, ranging from 37°C to 57°C, and exposure times of up to 2 h. The majority of protocols were focused on temperature and time permutations, where the response gradient was greatest. Post-treatment analysis by flow cytometry analysis was used to measure the incidences of apoptosis (annexin V-FITC stain), necrosis (propidium iodide (PI) stain), and HSP70 transcription (GFP expression). Cells grown in 3D compared with 2D culture showed reduced incidence of apoptosis and necrosis and a higher level of HSP70 expression in response to heat shock at the temperatures tested. Cells responded differently to hyperthermia when grown in 2D and 3D cultures. Three-dimensional culture appears to enhance survival plausibly by activating protective processes related to enhanced-HSP70 expression. These differences highlight the importance of selecting physiologically relevant 3D models in assessing cellular responses to hyperthermia in experimental settings.

Quantitative evaluation of the thermal heterogeneity on the surface of cryotherapy cooling pads.

We have investigated thermal operating characteristics of 13 commercially available cryotherapy units (CTUs) and their associated cooling pads using IR imaging. Quantitative examination of the temperature profiles from pad IR images shows diverse, nonuniform temperature distribution patterns. The extent of heterogeneity of the temperature fields was quantified via standard image analysis methods, including thresholding, spatial gradient diagrams, and frequency histogram distributions. A primary conclusion of this study is that it is a misnomer to characterize the thermal performance of a CTU and cooling pad combination in terms of a single therapeutic temperature.

50 years of computer simulation of the human thermoregulatory system.

This paper presents an updated and augmented version of the Wissler human thermoregulation model that has been developed continuously over the past 50 years. The existing Fortran code is translated into C with extensive embedded commentary. A graphical user interface (GUI) has been developed in Python to facilitate convenient user designation of input and output variables and formatting of data presentation. Use of the code with the GUI is described and demonstrated. New physiological elements were added to the model to represent the hands and feet, including the unique vascular structures adapted for heat transfer associated with glabrous skin. The heat transfer function and efficacy of glabrous skin is unique within the entire body based on the capacity for a very high rate of blood perfusion and the novel capability for dynamic regulation of blood flow. The model was applied to quantify the absolute and relative contributions of glabrous skin flow to thermoregulation for varying levels of blood perfusion. The model also was used to demonstrate how the unique features of glabrous skin blood flow may be recruited to implement thermal therapeutic procedures. We have developed proprietary methods to manipulate the control of glabrous skin blood flow in conjunction with therapeutic devices and simulated the effect of these methods with the model.

Recommended timing of medications that impact sleep and wakefulness: A review of the American Prescribers' Digital Reference.

An appreciable number of medicines have a recommended unique single time-of-day or asymmetrical or unequal-interval multiple-daily administration schedule. Many prescription and over-the-counter (OTC) products, according to administration time, can exert positive or negative impact on nighttime sleep and daytime wakefulness. Intuitively, medicines used to manage nighttime sleep and daytime wake disorders should be taken, respectively, at night before bedtime and morning after arising. However, some utilized for other medical conditions, if improperly timed, may compromise nocturnal sleep and diurnal attentiveness. We conducted a comprehensive review of the American Prescribers' Digital Reference, internet version of the Physician's Desk Reference, for the recommended scheduling of medications and OTC remedies that can impact sleep and wakefulness. The search revealed several hundred therapies of various classes -- α2-receptor agonists, antidepressants, barbiturates, central nervous system stimulants, benzodiazepines, dopamine agonists, dopamine norepinephrine reuptake inhibitors, selective norepinephrine reuptake inhibitors, eugeroics, γ-aminobutyric acid modulators, H1 and H3-receptor antagonists, melatonin analogues, OTC melatonin-containing products, non-benzodiazepine benzodiazepine-receptor agonists, dual orexin-receptor antagonists, and serotonin modulators -- that have a recommended unique dosing schedule. The tables and text of this article are intended to guide the proper scheduling of these medicines to optimize desired and/or minimize undesired effects.

Heat shock protein expression and temperature distribution in prostate tumours treated with laser irradiation and nanoshells.

PURPOSE: Sub-lethal temperature elevations in the tumour incurred during laser cancer therapy can induce heat shock protein (HSP) expression leading to enhanced tumour survival and recurrence. Nanoshells utilised in combination with laser therapy can potentially enable selective heat deposition, greater thermal injury, and diminished HSP expression in the tumour. The study objective was to measure the distribution of temperature and HSP expression in prostate tumours in response to laser therapy alone or with nanoshells to determine if these combinatorial therapies can minimise HSP expression. METHODS: PC3 cells were inoculated in the backs of CB17-Prkd c SCID/J mice and treated with external laser irradiation (wavelength of 810 nm, irradiance of 5 W/cm(2), spot size of 5 mm, and heating duration of 3 min) alone or in combination with gold nanoshells (diameter of 55 nm and outer gold shell thickness of 10 nm) introduced into the tumour 24 h prior to laser treatment. Magnetic resonance temperature imaging was used to measure the distribution of temperature elevation in the tumours during laser treatment. Tumours were sectioned 16 h following laser treatment, stained for Hsp27 and Hsp70, imaged with a confocal microscope, and HSP expression levels were quantified as a function of depth in the tumours. RESULTS: Maximum temperature elevations at the tumour surface were 28°C for laser treatment only and 50°C for laser heating in combination with gold nanoshells. Laser therapy alone caused significant induction of HSP expression in the first few millimeters of the tumour depth, whereas decreasing HSP expression occurred with greater tumour depth. Tumours treated with laser and nanoshells experienced substantial temperatures (73-78°C) at the tumour surface and temperatures greater than 53°C in the first few millimeters which eliminated HSP expression. CONCLUSION: Inclusion of nanoshells in laser therapy can provide a mechanism for enhancing heat deposition capable of eliminating HSP expression within a larger tumour region compared to laser heating alone.

A Conformable Two-Dimensional Resistance Temperature Detector for Measuring Average Skin Temperature.

Thermoregulation research and various medical procedures are accomplished by manipulating skin temperature in a nonuniform pattern. Skin temperature monitoring is essential to assess conformance to protocol specifications and to prevent thermal injury. Existing solutions for skin temperature monitoring include single point sensors, such as thermocouples, and two-dimensional methods of sensing surface temperature, such as infrared thermography, and wearable technology. Single point sensors cannot detect the average temperature and consequently their measurements cannot be representative of average surface temperature in a nonuniform temperature field. Infrared thermography requires optical access, and existing ambulatory sensors may require complex manufacturing processes and impede the heat exchange with a source by including a structural substrate layer. Our solution is a two-dimensional resistance temperature detector (two-dimensional (2D) RTD) created by knitting copper magnet wire into custom shapes. The 2D RTDs were calibrated, compared to one-dimensional sensors and wearable sensors, and analyzed for hysteresis, repeatability, and surface area conformation. Resistance and temperature were correlated with an R2 of 0.99. The 2D RTD proved to be a superior device for measuring average skin temperature over a defined area exposed to a nonuniform temperature boundary in the absence of optical access such as when a full body thermal control garment is worn.

The Circadian Rhythm of Thermoregulation Modulates both the Sleep/Wake Cycle and 24 h Pattern of Arterial Blood Pressure.

Borbély proposed an interacting two-component model of sleep regulation comprising a homeostatic Process S and a circadian Process C. The model has provided understanding of the association between core body temperature (CBT) as a key element of Process C that is deterministic of sleep onset and offset. However, it additionally provides a new perspective of the importance of the thermoregulatory mechanisms of Process C in modulating the circadian rhythm of arterial blood pressure (ABP). Herein, we examine the circadian physiology of thermoregulation, including at the end of the activity span the profound redistribution of cardiac output from the systemic circulation to the arteriovenous anastomoses of the glabrous skin that markedly enhances convective transfer of heat from the body to the environment to cause (i) decrease of the CBT as a pathway to sleep onset and (ii) attenuation of the asleep ABP mean and augmentation of the ABP decline (dipping) from the wake-time mean, in combination the strongest predictors of the risk for blood vessel and organ pathology and morbid and mortal cardiovascular disease events. We additionally review the means by which blood perfusion to the glabrous skin can be manipulated on demand by selective thermal stimulation, that is, mild warming, on the skin of the cervical spinal cord to intensify Process C as a way to facilitate sleep induction and promote healthy asleep ABP. © 2021 American Physiological Society. Compr Physiol 11:1-14, 2021.