Responses In Human Subjects Research Articles

Inert Gas Mild Pressure Action on Healthy Humans: The "IPA" Study.

The goal of this study was to evaluate inflammatory and oxidative stress responses in human subjects (9 females and 15 males) (age [29.6 ± 11.5 years old (mean ± SD)], height [172.0 ± 10.05 cm], and weight [67.8 ± 12.4 kg]) exposed to 1.45 ATA of helium (He) or nitrogen (N2) without concurrent hyperoxia. We hypothesized that elevated gas pressures would elicit an inflammatory response concurrent with oxidative stress. Consistent with ex vivo studies, both gasses elicited neutrophil activation, small elevations in microparticles (MPs) and increases in intra-MP interleukin (IL)-1β and inflammatory nitric oxide synthase, and an increase in urinary IL-6 concurrent with a marked reduction in plasma gelsolin. Mixed responses indictive of oxidative stress, with some biomarker elevations but little change in others and a decrease in some, were observed. Overall, these results demonstrate that exposure to typical diving gasses at a mildly elevated partial pressure will initiate inflammatory responses, which may play a significant role in decompression sickness (DCS). The complex pattern of oxidative stress responses may be indicative of competing systemic reactions and sampling different body fluids.

Acute hypoxic conditions preceding endotoxin administration result in an increased proinflammatory cytokine response in healthy men.

Tissues often experience hypoxia at sites of inflammation due to malperfusion, massive immune cell recruitment, and increased oxygen consumption. Organisms adapt to these hypoxic conditions through the transcriptional activation of various genes. In fact, there is significant crosstalk between the transcriptional responses to hypoxia and inflammatory processes. This interaction, named inflammatory hypoxia, plays a crucial role in various diseases including malignancies, chronic inflammatory lung diseases, and sepsis. To further elucidate the crosstalk between hypoxia and inflammation in vivo and assess its potential for innovative therapies, our study aimed at investigating the impact of acute hypoxic conditions on inflammation-induced immune responses. To this end, we exposed healthy human subjects to hypoxia either before (hypoxia priming) or after a single intravenous (i.v.) injection of 0.4 ng/kg LPS. Our data show that hypoxia exposure prior to LPS injection (hypoxia priming) amplified the proinflammatory response. This was reflected by an increase in body temperature, plasma noradrenaline levels, and the production of proinflammatory cytokines (i.e., IL-6 and TNF-α), compared with LPS control conditions. These effects were not observed when participants were exposed to hypoxia after LPS administration, demonstrating that the interaction between hypoxia and inflammation highly depends on the timing of both stimuli. Our findings suggest that acute hypoxia (i.e., hypoxia priming) modulates transient inflammation, leading to an enhanced proinflammatory response in healthy human subjects. This highlights the need for further investigations to understand the pathology of various hypoxia-inducible factor (HIF)-associated inflammatory diseases and to develop suitable, innovative therapies.NEW & NOTEWORTHY To our knowledge, this is the first in vivo study investigating the effects of hypoxia preceding (hypoxia priming) or following LPS administration on the endotoxin-induced inflammatory response in healthy human subjects. The data show that hypoxia priming amplified the proinflammatory response, reflected by an increased body temperature, increased plasma noradrenaline levels, and higher production of proinflammatory cytokines (i.e., IL-6 and TNF-α) compared with LPS control conditions.

Identification of human circulating factors following remote ischemic conditioning (RIC): Potential impact on stroke

Remote ischemic conditioning (RIC) is a procedure consisting of short cycles of ischemia applied in a limb that activates endogenous protection in distant organs, such as the brain. Despite the promising outcomes of RIC, the biochemical factors governing inter-organ communication remain largely unexplored, particularly in humans. A pilot study on 20 healthy humans was performed to identify potential circulating biochemical factors involved in RIC signalling. Blood was collected before and immediately, 4 and 22 h after the end of RIC. To characterize the responses triggered by RIC, a combination of biochemical and proteomic analysis, along with functional in vitro tests in human cells, were performed.RIC did not alter the levels of nitric oxide, bilirubin and cell-free mitochondrial DNA. In contrast, carboxyhaemoglobin levels increased following RIC at all time points and young subset, suggesting endogenous production of carbon monoxide that is a cytoprotective gasotransmitter. Additionally, the levels of glutathione and cysteinylglycine bound to proteins also increased after RIC, while glutathione catabolism decreased. Plasma proteomic analysis identified overall 828 proteins. Several steps of statistical analysis (Student's t-test, repeated measures ANOVA, with Holm corrected pairwise p-values <0.05 threshold and fold change higher or lower than 100 %) leaded to the identification of 9 proteins with altered circulating levels in response to RIC at 4h and 22h. All 9 proteins are from extracellular space or exosomes, being involved in inflammation, angiogenesis or metabolism control. In addition, RIC-conditioned plasma from young subjects protected microglial cell culture against inflammatory stimuli, indicating an anti-inflammatory effect of RIC. Nevertheless, other functional tests in neurons or endothelial cells had no effect. Overall, we present some evidence for RIC-induced anti-inflammatory and antioxidant responses in healthy human subjects, in particular in young subjects. This study is a first step towards the disclosure of signalling factors involved in RIC-mediated inter-organ communication.

Optical coherence tomography quantifies gradient refractive index and mechanical stiffness gradient across the human lens

BackgroundAs a key element of ocular accommodation, the inherent mechanical stiffness gradient and the gradient refractive index (GRIN) of the crystalline lens determine its deformability and optical functionality. Quantifying the GRIN profile and deformation characteristics in the lens has the potential to improve the diagnosis and follow-up of lenticular disorders and guide refractive interventions in the future.MethodsHere, we present a type of optical coherence elastography able to examine the mechanical characteristics of the human crystalline lens and the GRIN distribution in vivo. The concept is demonstrated in a case series of 12 persons through lens displacement and strain measurements in an age-mixed group of human subjects in response to an external (ambient pressure modulation) and an intrinsic (micro-fluctuations of accommodation) mechanical deformation stimulus.ResultsHere we show an excellent agreement between the high-resolution strain map retrieved during steady-state micro-fluctuations and earlier reports on lens stiffness in the cortex and nucleus suggesting a 2.0 to 2.3 times stiffer cortex than the nucleus in young lenses and a 1.0 to 7.0 times stiffer nucleus than the cortex in the old lenses.ConclusionsOptical coherence tomography is suitable to quantify the internal stiffness and refractive index distribution of the crystalline lens in vivo and thus might contribute to reveal its inner working mechanism. Our methodology provides new routes for ophthalmic pre-surgical examinations and basic research.

Intranasal M2SR (M2-deficient Single Replication) Influenza Vaccine Induces Broadly Reactive Mucosal Antibody Production in Adults.

Intranasal M2SR (M2-deficient Single Replication influenza virus) vaccine induces robust immune responses in animal models and human subjects. A high-throughput multiplexed platform was used to analyze hemagglutinin-specific mucosal antibody responses in adults after a single dose of H3N2 M2SR. Nasal swab specimens were analyzed for total and hemagglutinin-specific IgA. Significant, dose-dependent increases in mucosal antibody responses to vaccine-matched and drifted H3N2 hemagglutinin were observed in M2SR vaccinated subjects regardless of baseline serum and mucosal immune status. These data suggest that M2SR induces broadly cross-reactive mucosal immune responses which may provide better protection against drifted and newly emerging influenza strains.

Social setting interacts with hyper dopamine to boost the stimulant effect of ethanol.

Alcohol consumption occurring in a social or solitary setting often yields different behavioural responses in human subjects. For example, social drinking is associated with positive effects while solitary drinking is linked to negative effects. However, the neurobiological mechanism by which the social environment during alcohol intake impacts on behavioural responses remains poorly understood. We investigated whether distinct social environments affect behavioural responses to ethanol and the role of the dopamine system in this phenomenon in the fruit fly Drosophila melanogaster. The wild-type Canton-S (CS) flies showed higher locomotor response when exposed to ethanol in a group setting than a solitary setting, and there was no difference in females and males. Dopamine signalling is crucial for the locomotor stimulating effect of ethanol. When subjected to ethanol exposure alone, the dopamine transport mutant flies fumin (fmn) with hyper dopamine displayed the locomotor response similar to CS. When subjected to ethanol in a group setting, however, the fmn's response to the locomotor stimulating effect was substantially augmented compared with CS, indicating synergistic interaction of dopamine signalling and social setting. To identify the dopamine signalling pathway important for the social effect, we examined the flies defective in individual dopamine receptors and found that the D1 receptor dDA1/Dop1R1 is the major receptor mediating the social effect. Taken together, this study underscores the influence of social context on the neural and behavioural responses to ethanol.

High-protein, low glycemic index snack from optimized blend of three wholegrains exhibits nutraceutical quality and elicits low glycemic response in diabetic human subjects

Snack products are evolving as new carriers of functional ingredients with nutritional and health-promoting benefits. A blend of whole grains is increasingly being utilized to harness the functional potential of the grain mix. Amaranth, acha, and pearl millet grains flours were optimized using response surface methodology (RSM), to obtain optimum blends (90:5:5 and 47.98:26.68:25.34) with high protein content and low glycemic index. Snack bar products from the blends were labelled MBY and MBZ. A total of 40 diabetic and 10 non-diabetic subjects were recruited. Of the diabetic, about 42% were overweight while 40% were obese, the non-diabetic had normal weights. Each was allowed to consume snacks containing the equivalent of 50 g of carbohydrates. Finger prick was employed to evaluate the postprandial glucose response of snack products while venous blood was evaluated for antioxidant enzymes, carbohydrate-hydrolyzing activities, and insulin using standard methods. Consumption of the multigrain snacks elicited a stable postprandial response (133–141 mg/dL) with 16 and 24% postprandial decline. In addition, snacks had low to intermediate glycemic index (52 and 56) in diabetic and low glycemic index (43 and 45) in non-diabetics; likewise reduced α-amylase/α-glucosidase activities compared to control snacks. Similarly, glutathione level, glutathione peroxidase, superoxide dismutase, and catalase activities in serum from subjects that consumed multigrain snacks were upregulated compared to control and market sample groups. Moreso, snack products promoted a reduction in serum insulin levels in diabetic subjects (45 and 17% for MBY and MBZ respectively). Following the nutraceutical properties displayed by the formulated snack especially MBY, it can be promoted as a functional snack for the management of diabetes while solving the limited snack product choice of diabetes sufferers.Graphical

Evaluation of Seasonal Variations of Human Subjective Responses in China’s Cold Climate Zone

Evaluation of Seasonal Variations of Human Subjective Responses in China’s Cold Climate Zone

Injury Risk for the Hand and Forearm Under Loading Representative of Behind Shield Blunt Trauma.

Ballistic shields protect users from a variety of threats, including projectiles. Shield back-face deformation (BFD) is the result of the shield absorbing energy from a projectile and deforming towards the user. Back-face deformation can result in localized blunt loading to the upper extremity, where the shield is supported bythe user and may cause injury through behind armour blunt trauma (BABT) mechanisms. Post-mortem human subject (PMHS) responses are critical to identify the injury risk in these high-rate scenarios and are used to quantify the injury tolerance. Two vulnerable locations along the upper extremity were investigated-the hand and forearm-using eight PMHS to identify the fracture threshold resulting from shield BABT loading conditions. Impacts delivered to the hand at 16.4 ± 0.8m/s resulted in failure loads of 3818 ± 897N, whilst the forearm impacts delivered at a similar velocity of 16.9 ± 1.9m/s had lower failure loads at 3011 ± 656N. The corresponding 10% risk of hand and forearm fractures (as measured on a modified WorldSID Anthropomorphic Test Device) were identified as 11.0kN and 8.1kN, respectively, which should be used when evaluating future designs of composite ballistic shields. This study is the first known investigation of the upper extremity to this high loading rate scenario and provides the foundation for future biomechanical research in the area of behind shield blunt trauma.

Vestibular Testing-New Physiological Results for the Optimization of Clinical VEMP Stimuli.

Both auditory and vestibular primary afferent neurons can be activated by sound and vibration. This review relates the differences between them to the different receptor/synaptic mechanisms of the two systems, as shown by indicators of peripheral function-cochlear and vestibular compound action potentials (cCAPs and vCAPs)-to click stimulation as recorded in animal studies. Sound- and vibration-sensitive type 1 receptors at the striola of the utricular macula are enveloped by the unique calyx afferent ending, which has three modes of synaptic transmission. Glutamate is the transmitter for both cochlear and vestibular primary afferents; however, blocking glutamate transmission has very little effect on vCAPs but greatly reduces cCAPs. We suggest that the ultrafast non-quantal synaptic mechanism called resistive coupling is the cause of the short latency vestibular afferent responses and related results-failure of transmitter blockade, masking, and temporal precision. This "ultrafast" non-quantal transmission is effectively electrical coupling that is dependent on the membrane potentials of the calyx and the type 1 receptor. The major clinical implication is that decreasing stimulus rise time increases vCAP response, corresponding to the increased VEMP response in human subjects. Short rise times are optimal in human clinical VEMP testing, whereas long rise times are mandatory for audiometric threshold testing.

Social Allostasis Regulation by Robots

Social allostasis, the process by which social interactions dynamically regulate psychophysiological states (e.g., emotions), is attracting attention. Social allostasis can significantly impact people's mental and physical wellbeing. However, adaptive social relationships are not necessarily available to all people. The use of robots is expected to solve this problem. In this paper, we present three studies of our group that prove the influence of social interactions with robots on human psychophysiological states. Our results showed that robots could amplify human subjective and physiological emotional responses through conversation, touch, and television co-viewing experiences. These results suggest that robots may be helpful for adaptive social allostasis regulation.

Relaxin mechanistic effects on renal hemodynamics and natriuresis: a mathematical modeling approach

Relaxin (RLX) is a hormone that stimulates renal vasodilation during early pregnancy. Recombinant RLX may have potential as a treatment for heart failure and chronic kidney disease, but its application has been limited in part due to uncertainties about its mechanism of action, and particularly its effect on glomerular capillary hydrostatic pressure (P gc ) and fluid status. The objective of this study was to couple mathematical modeling with experimental observations of the renal hemodynamic and natriuretic response to RLX, in order to quantitatively describe the mechanistic effects of relaxin on the kidney, and to predict its effect on clinically difficult-to-measure variables such as P gc . Utilizing a previously developed mathematical model of kidney function and hemodynamics, we began by hypothesizing a minimum set of RLX mechanisms (afferent/efferent vasodilation), fitting the available hemodynamic/natriuretic response in two previously published rat studies (GFR, renal plasma flow (RPF), mean arterial pressure (MAP), sodium and water excretion), and adding additional RLX mechanisms to the model only when the minimal set could not explain available data. We found that changes in renal vascular resistances alone were sufficient to reproduce observed changes in RPF, but insufficient to explain other data features. Experimental studies reported much larger increases in sodium excretion relative to water excretion with RLX, and this effect could only be reproduced if an effect of RLX on the osmotic setpoint for vasopressin release was included in the model – a mechanism that has previously been reported in ovariectomized rats treated with RLX. A small effect of RLX on heart rate was necessary to produce observed changes in MAP.In addition, the single experimental study in which P gc has been measured with RLX reported a rise in GFR but fall in P gc , and this difference could not be explained mathematically by relative afferent/efferent dilation or by downstream shifting of the filtration equilibrium with increased RPF; it could only be reproduced mathematically if RLX was assumed to large positive effect on glomerular membrane permeability. However, the magnitude of this effect is difficult to justify physiologically. Thus, while the model can be forced to fit this limited data, further study is needed to understand whether and how RLX might have such large permeability effects.The fitted model was then able to make predictions consistent with observed renal responses in human subjects, and these effects were better predicted when the RLX effect on permeability was excluded, further suggesting that this effect may not be real. In these simulations, RLX had no net effect on P gc . In conclusion, while some uncertainty remains, this analysis suggests that RLX acts primarily by dilating the afferent and efferent arterioles and shifting the osmotic setpoint for vasopressin release. AstraZeneca and Eli Lilly This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of time-of-day on human dynamic thermal perception

Implementing heating and cooling set-point temperature modulations in buildings can promote energy savings and boost energy flexibility. However, time and time-of-day requirements in current indoor climate regulations are either overly simplified or ignored completely. A better understanding of how human thermal responses vary throughout the day is useful to effectively design and operate energy-flexible buildings. To date, only a handful of studies have looked at diurnal changes in thermal perception and mostly near steady-state neutrality without controlling for light exposure. This is the first experimental investigation aimed at understanding how the time of the day influences physiological and subjective human sensory responses to a localized dynamic thermal stimulus under constant light rich in long wavelengths (red). Results indicated that humans responded physiologically differently depending on the time of the day with a higher rate of change in the skin temperature in the evening compared with the afternoon. Furthermore, the increase of thermal sensation during the warming skin temperature transients was found to be greater in the evening. No differences were observed under steady-state thermal conditions. This evidence suggests that accounting for the time of the day is important when dynamically operating buildings, such as during demand-response programs.

Analysis of subjective thermal comfort data: A statistical point of view

Thermal comfort research aims to determine the relationship between the thermal environment and the human sense of warmth. This is usually achieved by measuring the subjective human thermal response to different thermal environments. However, it is common practice to use simple linear regression to analyse data collected using ordinal scales. This practice may lead to severe errors in inference. This study first set the methodological foundations to analyse subjective thermal comfort data from a statistical perspective. Subsequently, we show the practical consequences of fallacious assumptions by utilising a Bayesian approach and show, through an illustrative example, that a linear regression model applied to ordinal data suggests results different from those obtained using ordinal regression. Specifically, linear regression found no difference in means and effect size between genders, while the ordinal regression model led to the opposite conclusion. In addition, the linear regression model distorts the estimated regression coefficient for air temperature compared to the ordinal model. Finally, the ordinal model shows that the distance between adjacent response categories of the ASHRAE 7-point thermal sensation scale is not equidistant. Given the abovementioned issues, we advocate utilising ordinal models instead of metric models to analyse ordinal data.

Blockade Antibody Responses in Human Subjects Challenged with a New Snow Mountain Virus Inoculum.

Noroviruses (NoVs) are a leading cause of non-bacterial gastroenteritis in young children and adults worldwide. Snow Mountain Virus (SMV) is the prototype of NoV GII genotype 2 (GII.2) that has been developed as a viral model for human challenge studies, an important tool for studying pathogenesis and immune response of NoV infections and for evaluating NoV vaccine candidates. Previous studies have identified blockade antibodies that block the binding of NoV virus-like particles (VLPs) to histo-blood group antigens (HBGAs) as a surrogate for neutralization in human Norwalk virus and GII.4 infections but little is known about SMV blockade antibodies. In this secondary data analysis study, blockade antibodies were characterized in pre-challenge and post-challenge serum samples from human subjects challenged with a new SMV inoculum. The correlation between blockade antibody geometric mean antibody titers (GMTs) and SMV-specific serum IgG/IgA GMTs were examined after stratifying the subjects by infection status. A linear mixed model was applied to test the association between HBGA blockade antibody concentrations and post-challenge days accounting for covariates and random effects. Laboratory results from 33 SMV inoculated individuals were analyzed and 75.7% (25/33) participants became infected. Serum SMV-specific blockade antibodies, IgA, and IgG were all significantly different between infected and uninfected individuals beginning day 15 post-challenge. Within infected individuals, a significant correlation was observed between both IgG and IgA and blockade antibody concentration as early as day 6 post-challenge. Analysis of blockade antibody using the linear mixed model showed that infected individuals, when compared to uninfected individuals, had a statistically significant increase in blockade antibody concentrations across the post-challenge days. Among the post-challenge days, blockade antibody concentrations on days 15, 30, and 45 were significantly higher than those observed pre-challenge. The intraclass correlation coefficient (ICC) analysis indicated that the variability of blockade antibody titers is more observed between individuals rather than within subjects. These results indicate that HBGA-blockade antibody GMTs are generated after SMV challenge and the blockade antibodies were still detectable at day 45 post-challenge. These data indicate that the second-generation of SMV inoculum is highly effective.

Muscle activity on head-first compression responses of a finite element neck model

Effects of muscle activation on human neck kinematic responses under compressive loads have not been understood empirically due to the limitation of testing on in vivo test specimens. Advanced computational models can potentially provide information to improve our understanding of such responses. This study used a previously developed ligamentous finite element (FE) neck model, further integrated with muscles, fleshy tissue, and skin of the neck to predict the influence of passive and active muscles on responses to neck compression. For validation, post-mortem human subject (PMHS) and volunteer responses in frontal sled impacts were used to compare the dynamic response of the model with passive and active muscles, respectively. An objective evaluation of the validation responses suggested the ‘fair’ to ‘good’ biofidelity rating of the muscular system model. The compressive impacts, used to validate the ligamentous FE neck, were methodologically applied in the current study including the muscles with various activation states, flesh, and skin. The contribution of muscles (passive or active) resulted in an increase in the peak lower neck compression and shear forces and in a reduction in the upper neck forces on average; the role of active state dynamics of the muscles was crucial on the magnitude of the forces. Therefore, modeling of the muscles in a computational neck model may not be neglected to study a head-first compressive impact.

Four features of temporal patterns characterize similarity among individuals and molecules by glucose ingestion in humans

Oral glucose ingestion induces systemic changes of many blood metabolites related not only to glucose, but also other metabolites such as amino acids and lipids through many blood hormones. However, the detailed temporal changes in the concentrations of comprehensive metabolites and hormones over a long time by oral glucose ingestion are uncharacterized. We measured 83 metabolites and 7 hormones in 20 healthy human subjects in response to glucose ingestion. We characterized temporal patterns of blood molecules by four features: (i) the decomposability into “amplitude” and “rate” components, (ii) the similarity of temporal patterns among individuals, (iii) the relation of molecules over time among individuals, and (iv) the similarity of temporal patterns among molecules. Glucose and glucose metabolism-related hormones indicated a rapid increase, and citrulline and lipids, which indicated a rapid decrease, returned to fasting levels faster than amino acids. Compared to glucose metabolism-related molecules and lipids, amino acids showed similar temporal patterns among individuals. The four features of temporal patterns of blood molecules by oral glucose ingestion characterize the differences among individuals and among molecules.

Characterization of view in relation to solar-control systems

In this study, we developed a method to identify the affecting parameters that can characterize the view-out in relation to different solar-control systems. We hypothesize that the photometric composition, e.g., contrast, in the visual environment as a result of using solarcontrol systems impacts the subjective assessment of the view out. To test our hypothesis, we conducted user assessment studies where we measured objective photometric measurements and subjective human responses in a real semi-controlled environment. The user-assessment study was done with 51 participants. The participants were randomly allocated to a combination of five views out and six solar shading systems in a work environment where they answered questions related to the indoor environment and view quality. The relation between view and solar-control systems and their impact on the subjective assessment of view out was tested through the development of linear mixed-effects models. The models were developed using forward and backward selection and likelihood ratio test (LRT) to test the effects of adding or removing variables.Photometric quantities were measured as achromatic contrast and calculated both locally and globally, which are two different algorithms for the calculation of contrast as perceived by humans. Both were found to be significantly associated with respectively view rating and satisfaction and could be used to characterize the view-out quality through commonly used shading devices.

Human subjective responses and physiological parameters at different activity levels under solar irradiation

Human subjective responses and physiological parameters at different activity levels under solar irradiation

The synergy effect of temporal and spatial alliesthesia on occupants’ thermal comfort in air-conditioned temporarily occupied spaces (TOS)

Although the phenomena of temporal alliesthesia and spatial alliesthesia have been widely examined over the past few decades, the synergy effect of them on thermal comfort was seldom explored. In this work, human subjective responses were obtained from 16 acclimatized subjects (8 males & 8 females) to examine the synergy effect of temporal and spatial alliesthesia on thermal comfort. By regressing local skin temperatures and thermal sensation votes (TSVs), the goodness of fit R2 between skin temperatures to TSVs was determined. Quantitative analysis of the synergy effect of temporal alliesthesia and spatial alliesthesia in an air-conditioned temporarily occupied space (TOS) chamber was performed. Results showed that TSV (p < .05) and thermal comfort votes (TCVs) (p < .05) are better able to explain the temporal and spatial alliesthesia as compared to thermal preference votes (TPVs). The R2 between local skin temperature and TSVs at forehead (0.76), hand (0.74), thigh (0.80) and calf (0.83) were greater than that between local TSVs and mean radiant temperature (MRT) (0.63). The heating temperature setpoint might be reduced to 16 °C by the use of a non-adjustable heated chair in air-conditioned TOS to maintain the thermal comfort of guests (insulation: around 1.5 clo, metabolic rate: around 1.0 met, stay for less than 40 min). Meanwhile, occupants in the air-conditioned TOS chamber could maintain thermal comfort at 14 °C for half the time (25 min) that it does at 16 °C. The findings in this work might help achieve energy efficient thermal comfort and develop design guidelines for air-conditioned TOS equipped with heated chairs.