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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.)

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.

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.

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.

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.

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.

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.

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.