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Background: Esophageal carcinosarcoma (ECS) is a relatively rare malignancy, accounting for < 1% of all esophageal cancers. Its etiopathogenesis remains unknown. This study analyzed the genomic abnormalities in sarcomatous tumors from two patients undergoing subtotal esophagectomy using whole genome sequencing to elucidate the key characteristics of ECS., Case Presentation: We identified TP53 driver mutations, copy number gains in 11q13 (including CCND1), and Apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) signature enrichment in both ECS patients. Along with common genetic abnormalities, we identified CDKN2A driver mutations in case 1 and RAC1, NOTCH1, and TTC28 as novel fusion gene partners of MECOM in case 2. Notably, we detected germline pathogenic variant in Fanconi anemia (FA) complementation group I (FANCI) and group G (FANCG), which are involved in repairing DNA double-strand breaks by homologous recombination, for the first time, in ECS blood samples. These germline variants were truncating-type, Lys1221fs of FANCI (rs1567179036) for case 1 and Gln365Ter of FANCG (rs121434426) for case 2. We also identified somatic changes in cancer-associated pathways, such as PI3K/Akt/mTOR, cell cycle, and NOTCH signaling pathways, and structural chromosomal defects such as chromosome doubling., Conclusions: Our findings indicate that therapeutic drugs targeting the activation signal or FA pathway might be effective in treating ECS, however, their therapeutic significance should be elucidated in future studies., (© 2024. The Author(s).)

The fan cooling vest is coming into very common use by Japanese outdoor manual workers. We examined that to what extent using this vest reduces thermal strain and perception during outdoor exercise in the heat on a sunny summer day. Ten male baseball players in high school conducted two baseball training sessions for 2-h with (VEST) or without (CON) a commercially available fan cooling vest on a baseball uniform. These sessions commenced at 10 a.m. on separate days in early August. The fan airflow rate attached the vest was 62 L·s -1 . Neither ambient temperature (Mean ± SD: VEST 31.9 ± 0.2°C; CON 31.8 ± 0.7°C), wet-bulb globe temperature (VEST 31.2 ± 0.4°C; CON 31.4 ± 0.5°C) nor solar radiation (VEST 1008 ± 136 W·m -2 ; CON 1042 ± 66 W·m -2 ) was different between trials. Mean skin temperature (VEST 34.5 ± 1.1°C; CON 35.1 ± 1.4°C), infrared tympanic temperature (VEST 38.9 ± 0.9°C; CON 39.2 ± 1.2°C), heart rate (VEST 127 ± 31 bpm; CON 139 ± 33 bpm), body heat storage (VEST 140 ± 34 W·m -2 ; CON 160 ± 22 W·m -2 ), thermal sensation (- 4-4: VEST 0 ± 2; CON 3 ± 1) and rating of perceived exertion (6-20: VEST 11 ± 2; CON 14 ± 2) were lower in VEST than CON (all P < 0.05). Total distance measured with a global positioning system (VEST 3704 ± 293 m; CON 3936 ± 501 m) and body fluid variables were not different between trials. This study indicates that the fan cooling vest use can reduce thermal strain and perception during outdoor exercise in the heat on a sunny summer day. Cooling with this vest would be effective to mitigate thermal risks and perceptual stress in athletes and sports participants under such settings., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

Background: The gold standard for resectable, locally advanced esophageal squamous cell carcinoma (ESCC) is surgery-based treatment; however, it is unclear whether esophagectomy or chemoradiotherapy is suitable for older patients. This retrospective study aimed to identify the treatment outcomes of surgery-based therapy versus definitive chemoradiotherapy (dCRT) as an initial treatment for older patients with resectable, locally advanced ESCC., Methods: Data from 434 patients who received radical treatment for resectable, locally advanced ESCC were collected from January 2011 to December 2020. Of the patients >75 years of age, 49 underwent radical esophagectomy and 26 received dCRT. Survival was compared between the surgery and dCRT groups., Results: The mean ages of the surgery and chemoradiotherapy groups were 77.3 and 78.8 years, respectively. Differences in overall survival (OS) between the two groups were not statistically significant (3-year OS: surgery 66.2%, dCRT 55.7%, p = 0.236). Multivariate analysis for OS showed a hazard ratio of 1.229 for dCRT versus surgery (90% confidence interval 0.681-2.217). OS did not differ between the groups in any of the performance statuses. For patients who were able to receive chemotherapy using fluorouracil and cisplatin, OS tended to be better in the surgery group, but the difference was not statistically significant (3-year OS: surgery 68.1%, dCRT 51.8%, p = 0.117)., Conclusions: There was no clear difference in survival outcome between surgery-based therapy and dCRT as an initial treatment for esophageal cancer in older patients. Either treatment may be an option for older patients., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Introduction: There are no reports examining the time-of-day effect on team training sessions in the gym without airflow and air conditioning on thermal strain in the summer heat. We investigated this effect during badminton training sessions on a clear summer day., Methods: Nine male high school badminton players (Mean ± SD; age 17.1 ± 0.6 y, height 171 ± 4 cm, body mass 59 ± 7 kg) completed two 2.5-h badminton training sessions in the gym without airflow and air conditioning. The training sessions were started at 0900 h (AM) and 1600 h (PM) on separate days in August. Skin temperatures (chest, triceps, thigh, calf), infrared tympanic temperature, heart rate, thermal sensation and rating of perceived exertion were recorded at rest and at regular intervals during the sessions., Results: Indoor and outdoor environmental heat stress progressively increased in AM and decreased in PM during the sessions. Ambient temperature (AM 30.1 ± 0.9°C; PM 33.2 ± 1.0°C: P  < 0.001) and wet-bulb globe temperature (AM 28.1 ± 0.5°C; PM 30.0 ± 0.9°C: P  = 0.001) during the sessions in the gym were higher in PM than AM. Mean skin temperature (AM 34.2 ± 1.0°C; PM 34.7 ± 0.7°C: P  < 0.001), infrared tympanic temperature (AM 37.8 ± 0.5°C; PM 38.1 ± 0.4°C: P  = 0.001) and thermal sensation (AM 2.7 ± 1.4; PM 3.3 ± 1.0: P  < 0.001) during the sessions were higher in PM than AM. Body heat storage (AM 159 ± 30 W·m -2 ; PM 193 ± 30 W·m -2 : P  < 0.05) was greater in PM than AM. There were no time-of-day differences in the average heart rate (AM 75 ± 4% age-predicted maximal heart rate; PM 76 ± 5 age-predicted maximal heart rate: P  = 0.534), body mass loss (AM 0.6 ± 0.3 kg; PM 0.8 ± 0.2°C: P  = 0.079), the volume of water ingested (AM 1.5 ± 0.1 L; PM 1.6 ± 0.3 L: P  = 0.447) and rating of perceived exertion (AM 16 ± 2; PM 16 ± 3: P  = 0.281)., Conclusions: This study indicates greater thermal strain in PM trial than in AM trial during team training sessions in the gym without airflow and air conditioning on a clear summer day. Therefore, athletes and coaches of indoor sports should perceive that athletes may be exposed to a greater risk for thermal strain in the late afternoon from 1600 h than in the morning from 0900 h during the sessions in the gym under these conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Otani, Goto, Kobayashi, Goto, Shirato, Hosokawa, Tokizawa and Kaya.)

The present study examined the effect of wearing a water-soaked inner t-shirt with a ventilation garment on thermal and cardiovascular strain in eight young (26 ± 4 years) and eight older (67 ± 3 years) men undertaking moderate-intensity work (metabolic rate: 200-230 W m -2 ) in a hot environment (37°C, 50% RH, 2.8 kPa). While intermittent walking in hot conditions for 60 min, as a control (CON), the subject wore a dry inner t-shirt (long-sleeved) without fanning of a ventilation jacket (single-layered cotton, 0.21 clo). On separate days, under a fanned ventilation jacket, the subject wore a dry inner t-shirt (DRY) or an inner t-shirt soaked with 350 mL of tap water (WET). In the young group, increases in rectal temperature from pre-exercise baseline in the WET trial (0.7°C ± 0.2°C) were lower than in the CON (1.3°C ± 0.3°C) and DRY (1.1°C ± 0.2°C) (both p < 0.05) trials during exercise in hot conditions. In the older group, the increases were also attenuated in WET (0.7°C ± 0.4°C) compared with CON (1.3°C ± 0.4°C) and DRY (1.1°C ± 0.4°C) (both p < 0.05) without differences between age groups. Heart rate and whole-body sweat loss were lowest in the WET, followed by DRY, and then CON conditions in both groups (all p < 0.05). These findings demonstrate that wearing a water-soaked inner t-shirt while using a ventilation garment is an effective and practical cooling strategy to mitigate thermal and cardiovascular strains in young and older individuals during moderate-intensity work in hot conditions., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tokizawa.)

Objectives: We surveyed how home-working conditions, specifically furniture and computer use, affected self-reported musculoskeletal problems and work performance., Methods: Questionnaires from 4112 homeworkers were analyzed. The relationship between subjective musculoskeletal problems or work performance and working conditions were determined by logistic regression analyses., Results: More than half the homeworkers used a work desk, work chair, and laptop computer. However, approximately 20% of homeworkers used a low table, floor chair/floor cushion, or other furniture that was different from the office setup. Using a table of disproportionate size and height, sofa, floor cushion, and floor chair were associated with neck/shoulder pain or low back pain. Disproportionate table and chair, floor cushion, and tablet computer were associated with poor work performance., Conclusions: Disproportionate desk and chair, floor cushion/chair, and computer with small screen may affect musculoskeletal problems and home-working performance., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

This study aimed to evaluate the reliability of a patch-type sensor on the upper chest region that uses a dual-heat-flux method to estimate core temperature under various heat conditions. The participants' esophageal and rectal temperatures (T eso and T rec ) were measured with real-time monitoring of predicted core temperature (T pre ) using the patch. Twenty-one volunteers wearing work clothes and nine volunteers wearing protective clothing walked (5.0 km/h) for an hour at 35 °C. During exercise, T eso increased to 37.9 ± 0.3 °C and 38.2 ± 0.2 °C for each group, respectively. The root mean squared errors (RMSEs) were 0.18 ± 0.05 °C and 0.25 ± 0.08 °C between T eso and T pre and were 0.31 ± 0.10 °C and 0.34 ± 0.11 °C between T rec and T pre in each clothing condition, respectively. In addition, 11 volunteers walked for an hour at 30 °C or 40 °C. The T eso during exercise increased to 37.7 ± 0.3 °C and 38.2 ± 0.3 °C, respectively. The RMSEs were 0.23 ± 0.10 °C and 0.18 ± 0.05 °C between T eso and T pre in each ambient temperature condition, respectively. Furthermore, eight volunteers performed an arm-cranking exercise (60 W) for 30 min at 35 °C. The T eso increased to 37.9 ± 0.2 °C during exercise. The RMSEs were 0.22 ± 0.07 °C between T eso and T pre . The proportions of all paired measurements differing by less than the predefined threshold for validity of ≤ 0.3 °C were 85 ± 18% between T eso and T pre . These data indicate that the patch is capable of providing a moderate estimate of core temperature during low-intensity and acute exercise under heat conditions., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This study focused on everyday furniture and computers used in work from home and aimed to investigate how improper postures increase the risk of musculoskeletal disorders using different combinations of tables, chairs, and computers. Twenty-one healthy participants were asked to perform a visual display terminal task for 30 minutes in a laboratory modeled on the work from home concept. Seven experimental conditions were set up according to the different combinations of desks, chairs, and computers. Three-dimensional body posture was measured using a magnetic tracking device. The results showed that when using a low table, floor chair, and laptop computer, the body posture above the hip was similar to that when using a dining table, chair, and desktop computer. When using a sofa, and tablet computers, or laptop computer, severe neck flexion, which is stressful to the neck, was observed. Moreover, excessive low back flexion was observed when using a floor cushion and laptop computer. We suggest that computer work while sitting on a sofa or floor cushion without a backrest is harmful to the neck and low back.

Regular exercise maintains arterial endothelial cell homeostasis and protects the arteries from vascular disease, such as peripheral artery disease and atherosclerosis. Autophagy, which is a cellular process that degrades misfolded or aggregate proteins and damaged organelles, plays an important role in maintaining organ and cellular homeostasis. However, it is unknown whether regular exercise stimulates autophagy in aorta endothelial cells of mice prone to atherosclerosis independently of their circulating lipid profile. Here, we observed that 16 weeks of voluntary exercise reduced high-fat diet-induced atherosclerotic plaque formation in the aortic root of ApoE deficient mice, and that this protection occurred without changes in circulating triglycerides, total cholesterol, and lipoproteins. Immunofluorescence analysis indicated that voluntary exercise increased levels of the autophagy protein LC3 in aortic endothelial cells. Interestingly, human umbilical vein endothelial cells (HUVECs) exposed to serum from voluntarily exercised mice displayed significantly increased LC3-I and LC3-II protein levels. Analysis of circulating cytokines demonstrated that voluntary exercise caused changes directly relevant to IL-1 signaling (ie, decreased interleukin-1 receptor antagonist [IL-1ra] while also increasing IL-1α). HUVECs exposed to IL-1α and IL-1β recombinant protein significantly increased LC3 mRNA expression, LC3-I and LC3-II protein levels, and autophagy flux. Collectively, these results suggest that regular exercise protects arteries from ApoE deficient mice against atherosclerosis at least in part by stimulating endothelial cell autophagy via enhanced IL-1 signaling., (© 2021 Federation of American Societies for Experimental Biology.)

This study investigated the combined effects of different levels of solar radiation and airflow on endurance exercise capacity and thermoregulatory responses during exercise-heat stress. Ten males cycled at 70% peak oxygen uptake until exhaustion in an environmental chamber (30°C, 50% relative humidity). Four combinations of solar radiation and airflow were tested (800 W⋅m - 2 and 10 km⋅h - 1 [High-Low], 800 W⋅m - 2 and 25 km⋅h - 1 [High-High], 0 W⋅m - 2 and 10 km⋅h - 1 [No-Low], and 0 W⋅m - 2 and 25 km⋅h - 1 [No-High]). Participants were exposed to solar radiation by a ceiling-mounted solar simulator (Metal halide lamps) and the headwind by two industrial fans. Time to exhaustion was shorter (p < 0.05) in High-Low (mean ± SD; 35 ± 7 min) than the other trials and in High-High (43 ± 6 min) and No-Low (46 ± 9 min) than No-High (61 ± 9 min). There was an interaction effect in total (dry + evaporative) heat exchange which was less in High-Low and High-High than No-Low and No-High, and in No-Low than No-High (all p < 0.001). Core temperature, heart rate and thermal sensation were higher in high (High-Low and High-High) than no (No-Low and No-High) solar radiation trials and in lower (High-Low and No-Low) than higher (High-High and No-High) airflow trials (p < 0.05). Mean skin temperature and rating of perceived exertion were higher in high than no solar radiation trials (p < 0.05). This study indicates that combining high solar radiation and lower airflow have negative effects on thermoregulatory and perceptual strain and endurance exercise capacity than when combining high solar radiation and higher airflow and combining no solar radiation and lower/higher airflow during exercise-heat stress., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The time-of-day variations in environmental heat stress have been known to affect thermoregulatory responses and the risk of exertional heat-related illness during outdoor exercise in the heat. However, such effect and risk are still needed to be examined during indoor sports/exercises. The current study investigated the diurnal relationships between thermoregulatory strain and environmental heat stress during regular judo training in a judo training facility without air conditioning on a clear day in the heat of summer., Methods: Eight male high school judokas completed two 2.5-h indoor judo training sessions. The sessions were commenced at 09:00 h (AM) and 16:00 h (PM) on separate days., Results: During the sessions, indoor and outdoor heat stress progressively increased in AM but decreased in PM, and indoor heat stress was less in AM than PM (mean ambient temperature: AM 32.7±0.4°C; PM 34.4±1.0°C, P<0.01). Mean skin temperature was higher in AM than PM (P<0.05), despite greater dry and evaporative heat losses in AM than PM (P<0.001). Infrared tympanic temperature, heart rate and thermal sensation demonstrated a trial by time interaction (P<0.001) with no differences at any time point between trials, showing relatively higher responses in these variables in PM compared to AM during the early stages of training and in AM compared to PM during the later stages of training. There were no differences between trials in body mass loss and rating of perceived exertion., Conclusions: This study indicates a greater thermoregulatory strain in the morning from 09:00 h than the late afternoon from 16:00 h during 2.5-h regular judo training in no air conditioning facility on a clear day in the heat of summer. This observation is associated with a progressive increase in indoor and outdoor heat stress in the morning, despite a less indoor heat stress in the morning than the afternoon., Competing Interests: The authors have declared that no competing interests exist.

We present the case of a 75-year-old woman who received CapeOX plus Bmab therapy(capecitabine, oxaliplatin, and bevacizumab)after primary excision for an unresectable advanced sigmoid colon cancer with remote metastasis. Pneumatosis intestinalis(i.e., the presence of isolated gas in the abdominal cavity)was revealed accidentally during a periodical imaging examination in the small intestine and transverse colon, albeit no subjective symptoms were reported. Owing to the absence of definitive evidence of pneumatosis intestinalis and gastrointestinal perforation, the patient was diagnosed with idiopathic pneumatosis intestinalis. Bmab was discontinued, and CapeOX therapy alone was continued after follow-up. Approximately 4 months later, pneumatosis intestinalis had completely disappeared. Bmab is a vascular endothelial growth factor antibody with well-known side effect of gastrointestinal-perforation. However, there have been few reports on pneumatosis intestinalis; to our knowledge, there have been no reports on pneumatosis intestinalis associated with colorectal cancer in Japan. Further, the report suggests the need for appropriate and immediate management of pneumatosis intestinalis following diagnosis.

This study examined the effectiveness of a field-type liquid cooling vest (LCV) worn underneath an impermeable protective suit on heat strain during walking. Eight men walked for 60 min at a moderate speed (3.0 km/h) wearing the suit in a warm environment (33°C, 60% relative humidity) without (control, CON) or with the LCV. A smaller increase in rectal temperature was recorded in participants in the LCV than in the CON condition (37.6 ± 0.1°C vs. 37.9 ± 0.1°C, p<0.05). Walking while wearing the LCV reduced the level of physiological heat strain, as measured by the mean skin temperature (35.5 ± 0.1°C vs. 36.3 ± 0.1°C), chest sweat rate (13.5 ± 3.0 mg/cm 2 /h vs. 16.6 ± 3.8 mg/cm 2 /h), chest cutaneous vascular conductance (349 ± 88% vs. 463 ± 122%), body weight loss (0.72 ± 0.05% vs. 0.93 ± 0.06%), and heart rate (101 ± 6 beats/min vs. 111 ± 7 beats/min) (p<0.05, for all comparisons). These changes were accompanied by a decrease in thermal sensation and discomfort. These results suggest that a field-type LCV attenuates exertional heat strain while wearing impermeable protective clothing.

Chemokines are critical mediators of angiogenesis in several physiological and pathological conditions; however, a potential role for muscle-derived chemokines in exercise-stimulated angiogenesis in skeletal muscle remains poorly understood. Here, we postulated that the chemokine stromal cell-derived factor-1 (SDF-1α/C-X-C motif chemokine ligand 12: CXCL12), shown to promote neovascularization in several organs, contributes to angiogenesis in skeletal muscle. We found that CXCL12 is abundantly expressed in capillary-rich oxidative soleus and exercise-trained plantaris muscles. CXCL12 mRNA and protein were also abundantly expressed in muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α transgenic mice, which have a high proportion of oxidative muscle fibers and capillaries when compared with wild-type littermates. We then generated CXCL12 muscle-specific knockout mice but observed normal baseline capillary density and normal angiogenesis in these mice when they were exercise trained. To get further insight into a potential CXCL12 role in a myofiber-endothelial cell crosstalk, we first mechanically stretched C2C12 myotubes, a model known to induce stretch-related chemokine release, and observed increased CXCL12 mRNA and protein. Human umbilical vein endothelial cells (HUVECs) exposed to conditioned medium from cyclically stretched C2C12 myotubes displayed increased proliferation, which was dependent on CXCL12-mediated signaling through the CXCR4 receptor. However, HUVEC migration and tube formation were unaltered under these conditions. Collectively, our findings indicate that increased muscle contractile activity enhances CXCL12 production and release from muscle, potentially contributing to endothelial cell proliferation. However, redundant signals from other angiogenic factors are likely sufficient to sustain normal endothelial cell migration and tube formation activity, thereby preserving baseline capillary density and exercise training-mediated angiogenesis in muscles lacking CXCL12.

Background: Laparoscopic wedge resection (LWR) is widely performed for managing gastric submucosal tumors (SMTs). Despite the development of novel procedures such as laparoscopy-endoscopy cooperative surgery (LECS) and nonexposed endoscopic wall-inversion surgery (NEWS), the most appropriate surgical intervention for gastric SMTs remains unclear., Methods: We retrospectively reviewed patient characteristics, surgical outcomes, postoperative courses, results of histopathological examinations, and surgical costs of 71 consecutive patients who underwent LWR, LECS, or NEWS for gastric SMTs from January 2010 to June 2016 in our institute., Results: LWR, LECS, and NEWS were performed in 31, 14, and 26 cases, respectively. Patient backgrounds were comparable between groups. LWR was not performed for esophagogastric (E-G) junction tumors to avoid postoperative stricture, and LECS was not performed for ulcerated tumors to prevent tumor dissemination. NEWS was considered for tumors smaller than 3 cm for transoral extraction. Resected specimen area of the LWR group was significantly larger than that of the other groups. Further, the LWR group had a significantly higher complication rate. Compared to the LECS group, postoperative serum C-reactive protein level was significantly lower and postoperative hospitalization was significantly shorter in the NEWS group. Also, operation costs were significantly lower in the NEWS group., Conclusions: The surgical procedure for gastric SMTs must be carefully chosen according to tumor size, location, and presence or absence of ulceration. For selected patients, NEWS is suggested to be an appropriate option for the treatment of gastric SMTs.

cFos expression in the preoptic area (PO), which is thermoregulatory center increased by both heat and cold exposures; however, the regional difference is unknown yet. We aimed to determine if cFos expression in the PO was regionally different between heat and cold exposures. Mice were exposed to 27, 10, or 38°C for 90min, and body temperature (T b ) was measured. cFos-immunoreactive (cFos-IR) cells in the PO were counted by separating the PO into the ventral and dorsal parts in the rostral (bregma 0.38mm), central (-0.10mm), and caudal (-0.46mm) planes. T b at 10°C remained unchanged; however, it increased at 38°C. Counts of cFos-IR cells in all areas were greater at 38°C than at 27°C. In the dorsal and ventral parts of the central and the dorsal part of caudal PO, counts of cFos-IR cells were greater at 10°C than at 27°C. In conclusion, the areas of increased cFos expression in the PO in the heat were different that in the cold in mice., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The processes of thermoregulation are roughly divided into two categories: autonomic and behavioral. Behavioral thermoregulation alone does not have the capacity to regulate core temperature, as autonomic thermoregulation. However, behavioral thermoregulation is often utilized to maintain core temperature in a normal environment and is critical for surviving extreme environments. Thermal comfort, i.e., the hedonic component of thermal perception, is believed to be important for initiating and/or activating behavioral thermoregulation. However, the mechanisms involved are not fully understood. Thermal comfort is usually obtained when thermal stimuli to the skin restore core temperature to a regulated level. Conversely, thermal discomfort is produced when thermal stimuli result in deviations of core temperature away from a regulated level. Regional differences in the thermal sensitivity of the skin, hypohydration, and adaptation of the skin may affect thermal perception. Thermal comfort and discomfort seem to be determined by brain mechanisms, not by peripheral mechanisms such as thermal sensing by the skin. The insular and cingulate cortices may play a role in assessing thermal comfort and discomfort. In addition, brain sites involved in decision making may trigger behavioral responses to environmental changes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hyperosmolality in extracellular fluid in humans attenuates autonomic thermoregulation in heat, such as sweating and blood flow in the skin. However, exercise training minimizes the attenuation. The aim of the present study was to clarify the influence of hyperosmolality on thermal perception and to assess the training effect of exercise. Ten sedentary (SED) and 10 endurance-trained (TR) healthy young men were infused with 0.9% (normal saline [NS]) or 3% NaCl (hypertonic saline [HS]) for 120min on two separate days. After infusion for 20min, heat stimulus to the skin of the whole body was produced by a gradual increase in hot water-perfused suit temperature (33°C, 36°C, and 39°C), which was first used in the normothermic condition and then in the mild hyperthermic condition (0.5-0.6°C increase in esophageal temperature) and controlled by immersion of the lower legs in a water bath at 34.5°C and 42°C, respectively. Thermal sensation and comfort were rated at the time of each thermal condition. Plasma osmolality increased by ~10mosmL/kg·H2O in the HS trial. In the mild hyperthermic condition, increases in sweat rate and cutaneous vascular conductance were lower in the HS than in the NS trial in both the SED and TR groups (p<0.05). In the SED group, thermal sensation in the mild hyperthermic condition was lower in the HS than in the NS trial (p<0.05); there was no significant difference between the trials in the TR group. These results might indicate that hyperosmolality attenuates thermal sensation with heat and that exercise training eliminates the attenuation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

It has been speculated that the control of core temperature is modulated by physiological demands. We could not prove the modulation because we did not have a good method to evaluate the control. In the present study, the control of core temperature in mice was assessed by exposing them to various ambient temperatures (Ta), and the influence of circadian rhythm and feeding condition was evaluated. Male ICR mice (n=20) were placed in a box where Ta was increased or decreased from 27°C to 40°C or to -4°C (0.15°C/min) at 0800 and 2000 (daytime and nighttime, respectively). Intra-abdominal temperature (Tcore) was monitored by telemetry. The relationship between Tcore and Ta was assessed. The range of Ta where Tcore was relatively stable (range of normothermia, RNT) and Tcore corresponding to the RNT median (regulated Tcore) were estimated by model analysis. In fed mice, the regression slope within the RNT was smaller in the nighttime than in the daytime (0.02 and 0.06, respectively), and the regulated Tcore was higher in the nighttime than in the daytime (37.5°C and 36.0°C, respectively). In the fasted mice, the slope remained unchanged, and the regulated Tcore decreased in the nighttime (0.05 and 35.9°C, respectively), while the slopes in the daytime became greater (0.13). Without the estimating individual thermoregulatory response such as metabolic heat production and skin vasodilation, the analysis of the Ta-Tcore relationship could describe the character of the core temperature control. The present results show that the character of the system changes depending on time of day and feeding conditions., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: It is considered that sleep restriction is one of the risk factors for the development of exertional heat stroke and illness. However, how sleep restriction affects exertional heat strain and the nature of the coping strategy involved in this phenomenon remain unclear., Methods: Fourteen healthy subjects were studied on four occasions: after a night of normal sleep (NS, 7-8 h) and after a night of partial sleep restriction (PSR, 4 h), each with or without taking a daytime nap during the subsequent experimental day. The laboratory test consisted of two 40 min periods of moderate walking in a hot room in the morning and the afternoon., Results: The increase in rectal temperature during walking was significantly greater in PSR than in NS in the afternoon. The rating scores for physical and psychological fatigue and sleepiness were significantly greater in PSR than in NS, both in the morning and in the afternoon. The reaction times and lapses in the psychomotor vigilance task (PVT) after walking were significantly worse in PSR than in NS in the morning and after lunch. The nap intervention attenuated significantly the scores for fatigue and sleepiness in PSR. Furthermore, the decreased PVT response in PSR was significantly reversed by the nap., Conclusions: These results suggest that PSR augments physiological and psychological strain and reduces vigilance in the heat. Taking a nap seemed to be effective in reducing psychological strain and inhibiting the decrease in vigilance., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

We describe a patient with solitary lymph node (LN) metastasis after three endoscopic mucosal resections (EMRs) in which a gastrointestinal stromal tumor was difficult to differentiate from the carcinoid and lymphoma tumors. A 77-year-old man underwent three EMRs at 62, 72, and 75 years of age, and all resections were determined to be curative. However, 2 years after the last EMR, screening abdominal ultrasonography detected a 20-mm solitary tumor at the lesser curvature of the upper stomach. Laparoscopic tumor resection confirmed the pathological diagnosis. Intraoperative pathological diagnosis showed that the adenocarcinoma was compatible with recurrence of gastric cancer; thus, total gastrectomy with D1 lymphadenectomy was performed. Metastasis was not recognized by pathological examination but was detected by preoperative radiological examinations of the LN. We report a rare recurrence case after several EMRs of intramucosal gastric cancers.

This study compared heat strain during walking while wearing impermeable protective suits between fan-precooling and nonprecooling conditions. Six males engaged in 60 min of walking at a moderate speed (∼2.5 km/h) in a hot environment (37 °C, 40% relative humidity). Fanning using a fan (4.5 m/s) and spraying water over the body before wearing the suits produced significantly lower rectal temperature before the walking (37.3 ± 0.1 °C vs. 37.0 ± 0.1 °C, P < 0.05). In addition, whilst walking, rectal temperature was significantly lower in the precooling condition (maximum difference: 0.4 °C at 15 min of walking; 38.0 ± 0.1 °C vs. 37.8 ± 0.1 °C at the end of walking, P < 0.05). Although skin temperature decreased during fanning, no difference was observed during walking. Heart rate was lower in the precooling condition during the early stages of walking. Thermal and fatigue perceptions whilst walking did not differ between the conditions. Body weight loss was significantly lower in the precooling condition. These results may indicate that fan precooling attenuates exertional heat strain while wearing impermeable protective clothing. The fan-cooling method is practical, convenient, and yields lower heat strain during prolonged moderate exertion.

Cold defense mechanisms in mice are attenuated in the light phase during fasting, resulting in hypothermia. The present study examined whether specific neurons and areas in the SCN are related to the response. Mice were fasted over 47h or remained fed, during which they were placed at 20 or 27°C for 3h in the light or dark phases. Body temperature (Tb) was monitored. After the exposure, immunoreactive (IR) cells of cFos, arginine vasopressin (AVP), and vasoactive intestinal polypeptide (VIP) in the SCN were assessed. Tb at 20°C during fasting was lower in the light phase than in the dark phase. Both AVP/cFos-IR and VIP/cFos-IR cells increased when mice were at 20°C during fasting in the light phase. Such increase was observed in the central part of the SCN. These responses in the SCN may be related to the hypothermia in the light phase., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

In a previous study, we investigated the contribution of the surface of the face, chest, abdomen, and thigh to thermal comfort by applying local temperature stimulation during whole-body exposure to mild heat or cold. In hot conditions, humans prefer a cool face, and in cold they prefer a warm abdomen. In this study, we extended investigation of regional differences in thermal comfort to the neck, hand, soles, abdomen (Experiment 1), the upper and lower back, upper arm, and abdomen (Experiment 2). The methodology was similar to that used in the previous study. To compare the results of each experiment, we utilized the abdomen as the reference area in these experiments. Thermal comfort feelings were not particularly strong for the limbs and extremities, in spite of the fact that changes in skin temperature induced by local temperature stimulation of the limbs and extremities were always larger than changes that were induced in the more proximal body parts. For the trunk areas, a significant difference in thermal comfort was not observed among the abdomen, and upper and lower back. An exception involved local cooling during whole-body mild cold exposure, wherein the most dominant preference was for a warmer temperature of the abdomen. As for the neck and abdomen, clear differences were observed during local cooling, while no significant difference was observed during local warming. We combined the results for the current and the previous study, and characterized regional differences in thermal comfort and thermal preference for the whole-body surface.

Fasted mice show torpor-like hypothermia in the cold in their inactive phase. The aim of the present study was to elucidate whether leptin and/or ghrelin are involved in this reaction and to identify its neurophysiological mechanisms. In ob/ob mice, which lack leptin, metabolic heat production (oxygen consumption, Vo(2)) was suppressed in 20°C cold in both the light and dark phases, resulting in hypothermia. When wild-type mice received a systemic injection of 8 µg ghrelin in the early light phase, followed by a 2-h cold exposure to 10°C, their core body temperature (T(b)) decreased by 1.7°C, and they displayed a less marked increase in Vo(2) compared with vehicle-injected mice. However, ghrelin injection in the early dark phase resulted in the maintenance of T(b) and increased Vo(2) in the mice, which was similar to the result observed in the vehicle-injected mice. The number of doubly labeled neurons with cFos and neuropeptide Y (NPY) in the suprachiasmatic nucleus was greater in the light phase in the ghrelin-injected mice, which may suggest that ghrelin activates NPY neurons. On the contrary, in the paraventricular nucleus, the counts became greater only when they were exposed to the cold in the dark phase. These results indicate that ghrelin plays an important role in inducing time-dependent changes in thermoregulation in the cold via hypothalamic pathways.

Rats place their tails underneath their body trunks when cold (tail-hiding behavior). The aim of the present study was to determine whether this behavior is necessary to maintain body temperature. Male Wistar rats were divided into 'fed' and '42-h fasting' groups. A one-piece tail holder (8.4 cm in length) that prevented the tail-hiding behavior or a three-piece tail holder (2.8 cm in length) that allowed for the tail-hiding behavior was attached to the tails of the rats. The rats were exposed to 27°C for 180 min or to 20°C for 90 min followed by 15°C for 90 min with continuous body temperature and oxygen consumption measurements. Body temperature decreased by -1.0 ± 0.1°C at 15°C only in the rats that prevented tail-hiding behavior of the 42-h fasting group, and oxygen consumption increased at 15°C in all animals. Oxygen consumption was not different between the rats that prevented tail-hiding behavior and the rats that allowed the behavior in the fed and 42-h fasting groups under ambient conditions. These results show that the tail-hiding behavior is involved in thermoregulation in the cold in fasting rats.

We evaluated the effect of plasma hyperosmolality on behavioral thermoregulation in mice, using a new experimental system. The system consisted of Plexiglas box (dimensions: 50×12×19 cm) with five computer-controlled Peltier boards (dimensions: 10×10 cm) at the bottom. Experiments were conducted in two different settings of the system. An operant behavior setting: each board was first set to 39°C, and the right-end board was changed to 20°C for 1 min when a mouse moved to a specific position. A temperature mosaic setting: each board was randomly set to 15°C, 22°C, 28°C, 35°C, or 39°C with a 6-min interval, but each board temperature was different from the others at a given time point. Mice were injected subcutaneous (s.c.) isotonic or hypertonic saline (154 mM (IS group) or 2,500 mM (HS group), 10 ml/kg body wt), and exposed to either setting for 90 min. In the operant setting, the HS group showed fewer operant behavior counts than the IS group (11±5 and 25±4 counts, respectively; P<0.05) with greater increase in body temperature (1.6±0.4°C vs. 0.0±0.2°C, respectively; P<0.05). In the mosaic setting, the HS group selected the board temperature of 35°C more frequently than the other temperatures (P<0.05) with the same increase in body temperature. These results may suggest that plasma hyperosmolality modulates behavioral thermoregulatory response to heat and induce regulated hyperthermia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The present study elucidated the effects of habitual rowing exercise on arterial stiffness and plasma levels of the vasoconstrictor endothelin-1 and the vasodilator nitric oxide (NO) in older men. Eleven rowers (68.0 ± 1.6 years) and 11 sedentary control older men (64.9 ± 1.1 years) were studied. Peak oxygen uptake (36.0 ± 1.7 vs. 27.7 ±1.9 ml · kg(-1) · min(-1)), leg press power (1346 ± 99 vs. 1077 ± 68 W), and HDL-cholesterol (75 ± 5 vs. 58 ±3 mg · ml(-1)) were higher and triglyceride (78 ± 9 vs. 120 ± 14 mg · ml(-1)) was lower in rowers than in control participants (all P < 0.05). Arterial stiffness indices (carotid β-stiffness and cardio-ankle vascular index) and plasma endothelin-1 and NOx (nitrite + nitrate) levels did not differ between the two groups. These results suggest that habitual rowing exercise in older men is associated with high muscle power and aerobic capacity, and favourable blood lipid profile without affecting arterial stiffness or plasma levels of endotheline-1 and NO.

The present study examined the effect of the central administration of estrogen on responses to the cold. Estrogen or cholesterol was applied locally to the medial preoptic nucleus (MPO) or dorsomedial hypothalamic nucleus (DMH) of the hypothalamus in free-moving ovariectomized rats. Forty-eight hours after the application, rats had 2-h exposure at 10 or 25 degrees C. Body temperature (T(b)) and the tail surface temperature (T(tail)) were continuously measured by telemetry and thermography, respectively. The change of T(b) at 10 degrees C from the 25 degrees C baseline was higher in the estrogen application in the MPO than that in the cholesterol application; however, such difference was not observed in the DMH application. The uncoupling 1 protein mRNA level in the interscapular brown adipose tissue involved in non-shivering thermogenesis was not different between the estrogen and cholesterol applications in the MPO and DMH. T(tail) decreased in the cold, which was greater after the estrogen application in the MPO than after the cholesterol application. These results show that estrogen affects the MPO in female rats, changing T(b) in the cold. Moreover, suppression of heat loss from the tail may be involved in the mechanism., (Copyright 2010 Elsevier B.V. All rights reserved.)

Hypohydration caused by exercise in the heat attenuates autonomic thermoregulation such as sweating and skin blood flow in humans. In contrast, it remains unknown if behavioral thermoregulation is modulated during hypohydration. We assume that thermal unpleasantness could drive the behavioral response, and would also be modulated during hypohydration. Nine healthy young men participated in the present study. Body and skin temperatures were monitored. Ratings of thermal sensation and pleasantness were conducted. After approximately 45 min rest at 27 degrees C, they performed 50-min cycling exercise, which was at the level of 40% of heart rate range at 35 degrees C (hypohydration trial) or at the level of 10% of heart rate range at 23 degrees C (control trial), respectively. Subjects returned to the rest at 27 degrees C, and the ambient temperature was then changed from 22 to 38 degrees C. Body weight decreased by 0.9+/-0.1% immediately after exercise in the hypohydration trial and 0.3+/-0.1% in the control trial. In the cold, no significant difference in thermal sensation or pleasantness was observed between trials. There was no significant difference in thermal pleasantness between trials in the heat, although thermal sensation in the heat (32.5-36 degrees C) was significantly lower in the hypohydration trial than in the control trial. In addition, laser Doppler flow of the skin and sweat rate were attenuated in the heat in the hypohydration trial. These results may indicate that mild hypohydration after exercise in the heat has no influence on behavioral responses to the heat., ((c) 2010 Elsevier Inc. All rights reserved.)

The aim of this study was to determine whether estrogen modulates central and peripheral responses to cold in female rats. In ovariectomized female rats with and without administered estrogen [E(2) (+) and E(2) (-), respectively], the counts of cFos-immunoreactive cells in the medial preoptic nucleus (MPO) and dorsomedial hypothalamic nucleus (DMH) in the hypothalamus were greater in the E(2) (+) rats than in the E(2) (-) rats at 5 degrees C. Examination of the response of normal female rats to exposure to 5 degrees C at different phases of the estrus cycle revealed that counts of cFos-immunoreactive cells in the MPO, DMH, and posterior hypothalamus and the level of uncoupling protein 1 mRNA in the brown adipose tissues were greater in the proestrus phase than on day 1 of the diestrus phase. This result was linked to the level of plasma estrogen. The body temperature during cold exposure was higher in the E(2) (+) rats than in the E(2) (-) rats and was also higher in the proestrus phase than on day 1 of the diestrus phase. We conclude that estrogen may affect central and peripheral responses involved in thermoregulation in the cold.

To test the hypothesis that the dependence of the pressor response on muscle length is caused by changes in perfusion, we compared the cardiovascular responses to static contraction at short and long muscle lengths during free perfusion with those during circulatory arrest. Five males performed 2-min static knee extension exercise at 30% of maximal voluntary torque at each of two muscle lengths at a knee angle of 40 degrees (short) and 90 degrees (long). The subjects performed two trials - a free perfusion trial and a circulatory arrest trial. For circulatory arrest, an occlusion cuff placed around the proximal portion of the thigh was inflated to 250 mmHg 2 min before exercise. Mean arterial pressure (MAP), minute ventilation (V(E)), and the muscle oxygenation index in the vastus lateralis muscle were measured using near-infrared spectroscopy. In the free perfusion trial, MAP and V(E) were significantly greater during contractions at 90 degrees than at 40 degrees (p < 0.05). The muscle oxygenation index was significantly lower during contractions at 90 degrees than at 40 degrees (p < 0.05). Circulatory arrest diminished these differences. These results suggest that the relationship between muscle length and the pressor response can be explained by changes in perfusion, which are related to muscle length.

Our previous studies showed that venous occlusion or passive stretch of the lower limb, assuming a mechanical stimulus, attenuates the vasoconstriction in the non-exercised forearm during postexercise muscle ischaemia (PEMI) of the upper limb. In this study, we investigated whether a metabolic stimulus to the lower limb induces a similar response. Eight subjects performed a 2 min static handgrip exercise at 30% maximal voluntary contraction (MVC) followed by 3 min PEMI of the upper limb, concomitant with or without 2 min static ankle dorsiflexion at 30% MVC followed by 2 min PEMI of the lower limb. During PEMI of the upper limb alone, forearm blood flow (FBF) and forearm vascular conductance (FVC) in the non-exercised arm decreased significantly, whereas during combined PEMI of the upper and lower limbs, the decreases in FBF and FVC produced by PEMI of the upper limb was attenuated. Forearm blood flow and FVC were significantly greater during combined PEMI of the upper and lower limbs than during PEMI of the upper limb alone. When PEMI of the lower limb was released after combined PEMI of the upper and lower limbs (only PEMI of the upper limb was maintained continuously), the attenuated decreases in FBF and FVC observed during combined PEMI of the upper and lower limbs was not observed. Thus, forearm vascular responses differ when muscle metaboreceptors are activated in the upper limb and when there is combined activation of muscle metaboreceptors in both the upper and lower limbs.

This study compared cardiovascular responses to static extension and flexion exercises at four upper and lower limb joints. Eight males performed a 2 min static contraction at 30% of maximal voluntary torque followed immediately by 2 min post-exercise muscle ischaemia (PEMI) using each of four joints: the wrist, elbow, ankle, and knee. In the PEMI, an occlusion cuff placed around the proximal portion of the exercising muscle was inflated to 250 mmHg immediately before the cessation of exercise. Mean arterial pressure (MAP), heart rate (HR), calf blood flow, and calf vascular conductance (CVC) in the non-exercised calf were measured. There was a significant interaction for direction of movement (extension vs. flexion) and limb (upper vs. lower) in HR and CVC during both exercise and PEMI; extension in the wrist and elbow evoked a greater increase in HR and a greater decrease in CVC than flexion, whereas flexion in the ankle and knee elicited a greater increase in HR and a greater decrease in CVC than extension. These results suggest that the cardiovascular responses to extension and flexion differ between arms and legs, partly arising from the activation of the muscle metaboreflex.

To test whether changes in oxygenation of a resting skeletal muscle, evoked by a static contraction in a contralateral muscle, is uniform within a given skeletal muscle, we used near-infrared spectroscopy (NIRS). Seven subjects performed 2 min static knee extension exercise at 30% of maximal voluntary contraction. Changes in oxygenated hemoglobin (HbO(2)) were monitored using multiple-channel NIRS (40 channels, 13 sources and 12 detectors) attached on the contralateral nonexercising triceps surae muscle. Changes in HbO(2) were expressed as a percentage of total labile signals. To characterize the distribution of changes in HbO(2), channels were compared between their positions on the triceps surae muscle, and represented as 'proximal versus distal' and 'lateral versus medial' portions. During static muscle contraction, the averaged changes in HbO(2) of all channels were correlated with those in calf blood flow (plethysmography; R (2)=0.188, P<0.05) and with calf vascular conductance (R (2)=0.146, P<0.05). HbO(2) did not differ significantly between the lateral and medial portions of the triceps surae muscle. In contrast, the decrease of HbO(2) in the proximal portion of the muscle was greater than that of the distal portion (P<0.05). These results indicate that the changes in oxygenation of a resting muscle, evoked by static contraction of the contralateral muscle, are heterogeneous.

We examined the densities of adenosine A(2A) receptors in cardiac and skeletal muscles between untrained and endurance-trained subjects using positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]TMSX), a newly developed radioligand for mapping adenosine A(2A) receptors. Five untrained and five endurance-trained subjects participated in this study. The density of adenosine A(2A) receptors was evaluated as the distribution volume of [11C]TMSX in cardiac and triceps brachii muscles in the resting state using PET. The distribution volume of [11C]TMSX in the myocardium was significantly greater than in the triceps brachii muscle in both groups. Further, distribution volumes [11C]TMSX in the trained subjects were significantly grater than those in untrained subjects (myocardium, 3.6+/-0.3 vs. 3.1+/-0.4 ml g(-1); triceps brachii muscle, 1.7+/-0.3 vs. 1.2+/-0.2 ml g(-1), respectively). These results indicate that the densities of adenosine A(2A) receptors in the cardiac and skeletal muscles are greater in the endurance-trained men than in the untrained men.

We investigated whether selective muscle mechanoreceptor activation in the lower limb opposes arm muscle metaboreceptor activation-mediated limb vasoconstriction. Seven subjects completed two trials: one control trial and one stretch trial. Both trials included 2 min of handgrip and 2 min of posthandgrip exercise muscle ischemia (PEMI). In the stretch trial, a 2-min sustained triceps surae stretch, by brief passive dorsiflexion of the right foot, was performed simultaneously during PEMI. Mean arterial pressure, heart rate, and forearm blood flow (FBF) in the nonexercised arm and forearm vascular conductance (FVC) in the nonexercised arm were measured. During PEMI in the control trial, mean arterial pressure was significantly greater and FBF and FVC were significantly lower than baseline values (P < 0.05 for each). In contrast, FBF and FVC during PEMI in the stretch trial exhibited different responses than in the control trial. FBF and FVC were significantly greater in the stretch trial than in the control trial (FBF, 5.5 +/- 0.4 vs. 3.8 +/- 0.4 ml x 100 ml(-1) x min(-1); FVC, 0.048 +/- 0.004 vs. 0.033 +/- 0.003 unit, respectively; P < 0.05). These results indicate that passive triceps surae stretch can inhibit vasoconstriction in the nonexercised forearm mediated via muscle metaboreceptor activation in the exercised arm.

To test whether there is a regional difference in the exercise pressor reflex within a given muscle, we investigated the relationship between the inflection points of cardiovascular responses and muscle oxygenation during exercise. Seven subjects performed incremental exercise, which consisted of incremental 30-s static knee extensions, each separated by 30 s of recovery. The workload started at 5% maximal voluntary contraction (MVC) and increased by 5% MVC for each increment until exhaustion. Changes (Delta) in the concentrations (denoted by brackets) of oxygenated Hb (O2Hb) and deoxygenated Hb (HHb) were monitored in proximal and distal portions of the vastus lateralis by near-infrared spectroscopy. The inflection points of mean arterial pressure (MAP), calf vascular resistance (CVR), and muscle deoxygenation index (Delta[O2Hb-HHb]) were calculated as the intersection point of two regression equations obtained at lower and higher workloads. The inflection point of Delta[O2Hb-HHb] differed significantly between proximal and distal portions (28.5 +/- 3.0 vs. 39.5 +/- 3.0%MVC, P < 0.05). Linear regression analysis showed significant correlations between the inflection point of Delta[O2Hb-HHb] in the distal portion and MAP (r = 0.89; P < 0.01) and CVR (r = 0.89; P < 0.05), but no significant relationship between the inflection point in the proximal portion and MAP or CVR. These data show that the inflection point of muscle deoxygenation differs between proximal and distal portions within the vastus lateralis during incremental exercise and suggest that the distal portion of the vastus lateralis contributes more to the pressor response than does the proximal portion.