Evaluation of newly developed wearable ear canal thermometer, mimicking the application to activities on sports and labor fields.

We evaluated the reliability of a newly developed wearable ear canal thermometer based on three different experiments, in which ear canal and rectal temperature (Tear and Trec, respectively) were simultaneously monitored. In Experiment 1, participants sat at 28 °C and 50% relative humidity (RH), during which fanning or 41 °C lower legs water immersion was conducted. In Experiment 2, participants conducted a 70-min treadmill exercise (4 km/h, 0.5% slope) at 35 °C and 50% RH with intermittent fanning. In Experiment 3, participants completed a 20 min treadmill exercise (6 km/h, 5% slope) at 35 °C and 65% RH. Bland-Altman analysis for Tear and Trec showed the difference of - 0.2-0.3 °C and the limit of agreement of the mean ± 0.3-0.6 °C. The intraclass correlation coefficient was 0.44-0.83. The results may suggest that the ear canal thermometer is useful to assess core body temperature in sports and/or labor fields.

Characteristics of wet perception during the static touch of moist paper by the index fingertip alongside thermal stimulus application.

Several factors have been reported to affect the perception of wetness. In the present study, we aimed to examine how wet perception changes when the factors related to thermal and/or wetness stimuli are modulated. First, the percentage of participants experiencing wet perception among filter papers with different water contents (0.00, 3.75, 7.50, 11.25, 15.00, and 18.75 µg/cm2, corresponding to 0.00, 0.18, 0.37, 0.55,0.73 and 0.91 µg/mm3) was evaluated during static touch by the right index finger pad. The stimulus temperature was maintained at 30 °C. Second, the wet perception of paper with a water content of 18.75 µg/cm2 was evaluated at stimulus temperature of 20 °C, 25 °C, 30 °C, 35 °C, and 40 °C. In the first experiment, the percentage of participants experiencing wet perception elevated with the increasing water content; however, the percentage plateaued at 11.25 µg/cm2 of water (68.1 ± 25.5%). In the second experiment, when the stimulus temperature was < 30 °C, the wet perception increased as the stimulation temperature decreased. However, the wet perception reached a plateau at a stimulation temperature ≥30 °C. Participants experienced wet perception more consistently as the water content increased when the stimulus temperature was 30 ËšC. The effect of temperature on wet perception was limited to the stimulus temperature of <30 °C at which cold sensation was induced. However, no clear relationship between stimulus temperature and wet perception was observed when the stimulus temperature was ≥30 ËšC at which warm/hot sensation was induced.

Thermoregulatory heat-escape/cold-seeking behavior in mice and the influence of TRPV1 channels.

The present study assessed heat-escape/cold-seeking behavior during thermoregulation in mice and the influence of TRPV1 channels. Mice received subcutaneous injection of capsaicin (50 mg/kg; CAP group) for desensitization of TRPV1 channels or vehicle (control [CON] group). In Experiment 1, heat-escape/cold-seeking behavior was assessed using a newly developed system comprising five temperature-controlled boards placed in a cross-shape. Each mouse completed three 90-min trials. In the trials, the four boards, including the center board, were set at either 36˚C, 38˚C, or 40˚C, while one corner board was set at 32˚C, which was rotated every 5 min. In Experiment 2, mice were exposed to an ambient temperature of 37˚C for 30 min. cFos expression in the preoptic area of the hypothalamus (POA) was assessed. In Experiment 1, the CON group stayed on the 32˚C board for the longest duration relative to that on other boards, and intra-abdominal temperature (Tabd) was maintained. In the CAP group, no preference for the 32˚C board was observed, and Tabd increased. In Experiment 2, cFos expression in the POA decreased in the CAP group. Capsaicin-induced desensitization of TRPV1 channels suppressed heat-escape/cold-seeking behavior in mice during heat exposure, resulting in hyperthermia. In conclusion, our findings suggest that heat sensation from the body surface may be a key inducer of thermoregulatory behaviors in mice.

Differences in the neural networks of thermal sensation with and without evaluation process.

Several neuroimaging studies have analyzed the neural networks involved in thermal sensation. In some of these studies, participants were instructed to evaluate and report the thermal sensation using a point scale, visual analog scale, or other psychophysical rating tool while the imaging data were obtained. Therefore, the imaging data may reflect signals involved in the processes of both sensation and evaluation. The present study aimed to discriminate the neural networks involved in identifying different temperature stimuli and the two different processes by using functional magnetic resonance imaging (fMRI). We applied four different thermal stimuli ("hot," 40C; "warm," 36 °C, "cool," 27 °C; and "cold," 22 °C) to the left forearm using Peltier apparatus. During the stimuli, participants were instructed to either evaluate (evaluation task) or not evaluate (no-evaluation task) and report the thermal sensation. We found brain activation in the medial prefrontal cortex/anterior cingulate gyrus, inferior frontal gyrus, bilateral insula, and posterior parietal cortex during the four thermal stimuli both with and without the evaluation task. Additionally, the stimuli with the evaluation task induced stronger and broader activation, including the right fronto-parietal and anterior insula regions. These results indicate that thermal stimulation activates the common neural networks, independent of the thermal conditions and evaluation process. Moreover, the evaluation process may increase the attention to the thermal stimuli, resulting in the activation of the right lateralized ventral attentional network.

Surgical masks do not increase the risk of heat stroke during mild exercise in hot and humid environment.

Surgical masks are widely used for the prevention of respiratory infections. However, the risk of heat stroke during intense work or exercise in hot and humid environment is a concern. This study aimed to examine whether wearing a surgical mask increases the risk of heat stroke during mild exercise in such environment. Twelve participants conducted treadmill exercise for 30 min at 6 km/h, with 5% slope, 35°C ambient temperature, and 65% relative humidity, while wearing or not a surgical mask (mask and control trials, respectively). Rectal temperature (Trec), ear canal temperature (Tear), and mean skin temperature (mean Tskin) were assessed. Skin temperature and humidity of the perioral area of the face (Tface and RHface) were also estimated. Thermal sensation and discomfort, sensation of humidity, fatigue, and thirst were rated using the visual analogue scale. Trec, Tear, mean Tskin, and Tface increased during the exercise, without any difference between the two trials. RHface during the exercise was greater in the mask trial. Hot sensation was greater in the mask trial, but no influence on fatigue and thirst was found. These results suggest that wearing a surgical mask does not increase the risk of heat stroke during mild exercise in moist heat.

Identification of Thiazoyl Guanidine Derivatives as Novel Antifungal Agents Inhibiting Ergosterol Biosynthesis for Treatment of Invasive Fungal Infections.

Invasive fungal infections (IFIs) are fatal infections, but treatment options are limited. The clinical efficacies of existing drugs are unsatisfactory because of side effects, drug-drug interaction, unfavorable pharmacokinetic profiles, and emerging drug-resistant fungi. Therefore, the development of antifungal drugs with a new mechanism is an urgent issue. Herein, we report novel aryl guanidine antifungal agents, which inhibit a novel target enzyme in the ergosterol biosynthesis pathway. Structure-activity relationship development and property optimization by reducing lipophilicity led to the discovery of 6h, which showed potent antifungal activity against Aspergillus fumigatus in the presence of serum, improved metabolic stability, and PK properties. In the murine systemic A. fumigatus infection model, 6h exhibited antifungal efficacy equivalent to voriconazole (1e). Furthermore, owing to the inhibition of a novel target in the ergosterol biosynthesis pathway, 6h showed antifungal activity against azole-resistant A. fumigatus.

Influence of exogenous and endogenous estrogen on thermoregulatory responses to mild heat and the interaction with light and dark phases.

The present study aimed to determine the influence of estradiol (E2) and the interaction with circadian phases on thermoregulatory responses to mild heat in female rats. Heat loss and production during 3-h exposure to the environment at an ambient temperature of 28-34 °C were assessed by measuring abdominal temperature (Tabd), tail skin temperature, and oxygen consumption in ovariectomized rats with and without E2 replacement (OVX + E2 and OVX, respectively) and in control rats in the proestrus (P) and diestrus (D) phases. In the light phase, Tabd remained unchanged in all groups. Tabd increased in the dark phase, but was lower in the OVX + E2 and P groups than in the OVX and D groups. Oxygen consumption decreased at 34 °C, but to a lesser extent in the OVX + E2 group than in the OVX group. These results suggest that E2 activates thermoregulation in mild heat in the dark phase.

Thermal and cardiovascular responses and thermal sensation during hot-water bathing and the influence of room temperature.

The aim of the present study was to clarify physical risks during hot-water bathing by measuring thermal and cardiovascular responses and thermal sensation. Young men and women (n = 7 and 5, respectively) participated in the present study, which consisted of two trials mimicking bathing behavior at room temperature of 25 °C and 15 °C. Participants bathed in 41 °C water for 20 min to the subclavian level. Before bathing, participants rested fully clothed for 15 min and then rested for 15 min without clothes. After bathing, they rested without clothes for 15 min and afterwards rested fully clothed for another 15 min. Tympanic temperature (Tty), heart rates (HR), mean skin temperature (Tsk), mean arterial pressure (MAP), and laser-Doppler flow at the chest and forehead (LDFhead and LDFchest) were evaluated. Thermal perception was assessed with a visual analogue scale. Mean Tsk in the 15 °C trial decreased during the period without clothing while MAP increased. The value remained unchanged in the 25 °C trial. During bathing, Tty, mean Tsk, HR, LDFhead, and LDFchest increased in both trials, and MAP decreased to similar levels. Relative change in LDFchest was greater in the 15 °C trial than in the 25 °C trial. Participants felt cold when they were without clothes at 15 °C; however, the thermal perception during bathing was similar between the two trials. Greater changes in cardiovascular and thermal responses were observed during the bathing behavior. In addition, bathing in cold room augmented the changes, which may induce some physical risks during bathing.

Potent oxazolidinone antibacterials with heteroaromatic C-ring substructure.

Novel oxazolidinone analogues bearing a condensed heteroaromatic ring as the C-ring substructure were synthesized as candidate antibacterial agents. Analogues 16 and 21 bearing imidazo[1,2-a]pyridine and 18 and 23 bearing [1,2,4]triazolo[1,5-a]pyridine as the C-ring had excellent in vitro antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis (VRE), and penicillin-resistant Streptococcus pneumoniae (PRSP). They also showed promising therapeutic effects in a mouse model of lethal infection. Preliminary safety data (inhibitory effects on cytochrome P450 isoforms and monoamine oxidases) were satisfactory. Further evaluation of 18 and 23 is ongoing.

Total synthesis of mappicine ketone (nothapodytine B) by means of sulfur-directed 5-exo-selective aryl radical cyclization onto enamides.

Enamides 5, on treatment with Bu(3)SnH-AIBN, underwent aryl radical cyclization in a 5-exo manner to give 1-[bis(phenylthio)methyl]dihydroisoindoles 6, which were partially desulfurized with Bu(3)SnH-AIBN to give 1-mono(phenylthio)methyl congeners 7. Formation of 6 from 5 may be explained by the presence of two phenylthio groups at the terminus of the N-vinylic bond of 5, since enamide 8a having no phenylthio group underwent aryl radical cyclization in a 6-endo manner. Compound 7d (R = CF(3)) was transformed into sulfoxide 16, which was treated with (CF(3)CO)(2)O and then with 10% NaOH to give a model compound 20 of mappicine ketone (MPK) (1) through aldol condensation of aldehyde 18. An attempt to synthesize MPK using this method with sulfoxide 28 prepared from 25, however, was unsuccessful, and, instead, photochemical cyclization of enamide 38 prepared from 25 furnished MPK.