Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

Background/Aims: The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response. Methods: In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled. Results: Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response. Conclusions Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

Purpose: This study aimed to investigate changes in target coverage using magnetic resonance–guided online adaptive radiotherapy (MRgoART) for kidney tumors and to evaluate the suitable timing of treatment. Materials and Methods: Among patients treated with 3-fraction MRgoART for kidney cancer, 18 tumors located within 1 cm of the gastrointestinal tract were selected. Stereotactic radiosurgery planning with a prescription dose of 26 Gy was performed using pretreatment simulation and three MRgoART timings with an adapt-to-shape method. The best MRgoART plan was defined as the plan achieving the highest percentage of planning target volume (PTV) coverage of 26 Gy. In clinical scenario simulation, MRgoART plans were evaluated in the order of actual treatment. Waiting for the next timing was done when the PTV coverage of 26 Gy did not achieve 95%–99% or did not increase by 5% or more compared to the pretreatment plan. Results: The median percentages of PTV receiving 26 Gy in pretreatment and the first, second, and third MRgoART were 82% (range, 19%), 63% (range, 7% to 99%), 88% (range, 31% to 99%), and 95% (range, 3% to 99%), respectively. Comparing pretreatment simulation plans with the best MRgoART plans showed a significant difference (p = 0.025). In the clinical scenario simulation, 16 of the 18 planning series, including nine plans with 95%–99% PTV coverage of 26 Gy and seven plans with increased PTV coverage by 5% or more, would be irradiated at a good timing. Conclusion MRgoART revealed dose coverage differences at each MRgoART timing. Waiting for optimal irradiation timing could be an option in case of suboptimal timing.

BACKGROUND: Neck cooling is a practical method for preventing heat-related illness, however, its effectiveness in general workers is not well established. This study aimed to assess the effects of neck cooling on core body temperature and other physiological markers during exercise in a hot environment. METHODS: This randomized crossover trial was conducted from November 2023 to April 2024 at the Shared-Use Research Center at UOEH. Fourteen healthy adult males participated in the study under two conditions: with neck cooling (COOL) and without neck cooling (CON). All participants completed both conditions, and the order of condition assignment was determined by a random draw. Participants first rested for 10 minutes in a 28.0 °C, 50% relative humidity environment, followed by a rest in a 35.0 °C, 50% relative humidity environment for another 10 minutes. In the COOL condition, participants wore a neck cooler containing 1,200 g of ice while exercising at 50% Heart Rate Reserve on a bicycle ergometer for 20 minutes. Afterward, they rested for 15 minutes in the hot environment while still wearing the cooler. MAIN OUTCOME MEASURES: Core body temperature (rectal and esophageal), forehead skin temperature, and heart rate were continuously monitored and compared using a mixed model. Estimated sweat volume was calculated based on changes in body weight before and after the experiment. RESULTS: At the end of the rest period, no significant differences were observed between the COOL and CON conditions in rectal temperature (37.76 ± 0.18 °C versus 37.75 ± 0.24 °C, p = 0.9493), esophageal temperature (37.75 ± 0.30 °C versus 37.76 ± 0.23 °C, p = 0.7325), forehead skin temperature (36.87 ± 0.29 °C versus 36.88 ± 0.27 °C, p = 0.2160), or heart rate (104.18 ± 7.56 bpm versus 107.52 ± 7.40 bpm, p = 0.1035). Estimated sweat loss was similar between conditions (578 ± 175 g for CON versus 572 ± 242 g for COOL, p = 0.5066). While more participants felt cooler in the COOL condition, RPE showed no significant difference. CONCLUSION Neck cooling did not significantly affect core temperature or perceived exertion. Maintaining close contact with the skin at sufficiently low temperatures or utilizing cooling methods that prevent excessive negative feedback may be necessary to enhance the effectiveness of neck cooling.
Humans ; Male ; Cross-Over Studies ; Exercise/physiology* ; Adult ; Neck/physiology* ; Hot Temperature/adverse effects* ; Young Adult ; Body Temperature ; Heart Rate ; Skin Temperature ; Body Temperature Regulation ; Cold Temperature

Background: Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) has been recognized as an effective treatment for patients at high risk for surgery. An antimigration metal stent with tapered thin delivery system has recently been developed. The aims of this study were to evaluate the feasibility, safety, and longterm outcomes of EUS-GBD using the new metal stent. Methods: Between April 2017 and March 2020, 21 patients with acute cholecystitis unsuitable for cholecystectomy underwent EUS-GBD using the metal stent. The stent was 6 mm in diameter and 6 cm in length, with a large flare at both ends for antimigration, and mounted in a 7.5 Fr delivery catheter, which requires no dilation devices. We retrospectively evaluated clinical and technical success, adverse events, and stent patency. Results: The technical and clinical success rates of EUS-GBD using the metal stent were 95.2% and 100%, respectively. For 75% of the patients, metal stents could be placed without dilatation of the needle tract. These patients had significantly shorter procedure time (23.6 ± 9.8 min) than patients requiring needle tract dilatation (38.4 ± 17.1 min; P = 0.036). The median follow-up periods were 336 days (interquartile range [IQR] 152–919 days) and 1,135 days (IQR 1,009–1,675 days) for all and alive patients, respectively. No adverse events or recurrence of cholecystitis due to stent occlusion that occurred in any patient at follow-up was observed. Conclusion In conclusion, EUS-GBD using the newly designed metal stent showed excellent safety and longterm outcomes, and may be suitable as an alternative treatment in patients who are unsuitable for cholecystectomy.

Purpose: Urinary incontinence (UI) is a significant complication following surgery for pelvic organ prolapse (POP), including laparoscopic sacrocolpopexy (LSC). Although the incidence of postoperative UI is lower after LSC than after transvaginal mesh surgery, a subset of patients still experience UI. This study aimed to determine which factors, including mesh-related factors, contribute to UI impairing daily life following LSC. Methods: The study enrolled 96 patients who underwent LSC at our institution between June 2016 and September 2023. The Pearson chi-square test, multiple logistic regression analysis, and Cox proportional hazards model were used to determine the independent factors contributing to UI after LSC. Results: The Pearson chi-square test showed that body mass index, POP quantification (POP-Q) stage 4 and the presence of preoperative UI significantly correlated with the postoperative UI among preoperative and intraoperative factors (all P<0.05). POP-Q stage 4 and the presence of preoperative UI were also significant factors in both univariate and multivariate analyses of multiple logistic regression analysis (all P<0.05). However, only preoperative UI remained an independent predictor for shorter time to UI onset in the multivariate Cox proportional hazards model (hazard ratio, 3.56; 95% confidence interval, 1.29–11.58; P=0.0158). Conclusions Patients with preoperative UI and stage 4 POP should receive close monitoring for postoperative UI.