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.

Introduction: In patients receiving opioids, relief of cancer pain by palliative radiation therapy or other means can lead to opioid discontinuation and subsequent withdrawal symptoms, such as agitation, insomnia, and diarrhea, due to opioid-related physical dependence. Appropriate steps should be taken to prevent these symptoms. Case: A 72-year-old man underwent surgery for esophageal cancer. He developed low back pain and right lower limb pain, and was diagnosed with sacral and right iliac bone metastases. His pain was resistant to oxycodone (OXC), so he was simultaneously treated with methadone (MDN) and palliative radiotherapy. His pain gradually decreased, and MDN was tapered and switched to OXC, which was in turn discontinued at 20 mg/day at the patient's strong request. After OXC discontinuation, akathisia, anxiety, and diarrhea appeared as withdrawal symptoms. These were treated with immediate-release OXC, transdermal fentanyl, and suvorexant. Discussion: When discontinuing opioids, dose reduction below 10% per week is recommended, de-escalation to the lowest possible dose should be followed by cessation. In case of withdrawal symptoms, immediate-release opioids may be used, and opioid tapering should be attempted in parallel with symptom control.

A certain period of time has passed since the transition to the General Medicine residency system under the Japanese Medical Specialty Board and Family Medicine specialist training system by the Japan Primary Care Association. We have summarized the needs of residents identified in the survey, and detailed the activities to date and prospects of the Japanese Association of Family Physician Trainees, a self-help support organization, which is an official subcommittee of the Japan Primary Care Association, from the viewpoint of the residents. We believe that this paper will serve as a resource for the training of residents, help guide them under the new system, and help to improve the training system, considering evidence suggesting that information may not be reaching residents who need support.

Background/Aims: Endoscopic biliary drainage is the gold standard treatment for cholangitis. The two methods of biliary drainage are endoscopic biliary stenting and nasobiliary drainage. A novel integrated outside biliary stent and nasobiliary drainage catheter system (UMIDAS NB stent; Olympus Medical Systems) was recently developed. In this study, we evaluated the efficacy of this stent in the treatment of cholangitis caused by common bile duct stones or distal bile duct strictures. Methods: We conducted a retrospective pilot study by examining the medical records of patients who required endoscopic biliary drainage for cholangitis due to common bile duct stones or distal bile duct strictures, and who were treated with a UMIDAS NB stent, between December 2021 and July 2022. Results: Records of 54 consecutive patients were reviewed. Technical and clinical success rates were 47/54 (87.0%) and 52/54 (96.3%), respectively. Adverse events were observed in 12 patients, with six patients experiencing pancreatitis as an adverse event, following endoscopic retrograde cholangiopancreatography (ERCP). Regarding late adverse events, five cases of biliary stent migration into the bile duct were observed. Disease-related death occurred in one patient. Conclusions The outside-type UMIDAS NB stent is an efficacious new method for biliary drainage and can be applied to many indications.

A 76-year-old female was admitted with complaints of dyspnea on exertion and lower leg edema. She had undergone an aortic valve replacement thirty-nine years before and a redo aortic valve replacement and mitral valve replacement twenty-eight years before. She also had hemolytic anemia with jaundice. Echocardiography showed severe paravalvular leakage in the aortic and mitral valves, and a blood flow in the aortic annulus that flows from the aortic side into the left atrium. We diagnosed heart failure and hemolytic anemia due to paravalvular leakage and decided to perform a double-valve replacement for the third time. On operation, after removing the aortic valve through aortotomy, aorto- mitral fibrous continuity was extensively calcified and perforated, and its strength was not enough to sew the prosthetic valve to it. Therefore, we decided to perform the Commando procedure. Aortotomy was extended between the noncoronary aortic sinus and the left coronary aortic sinus until it reached the dome of the left atrium. After the prosthetic mitral valve was excised, annuloplasty of the posterior mitral annulus was performed using a bovine pericardial patch, and the new prosthesis mitral valve was implanted. The anterior part of the annulus corresponding to the aorto-mitral fibrous continuity was reconstructed by sewing the base of a two-tongued triangular bovine pericardial patch to the sewing cuff of the mitral prosthesis. After closing the left atrial ceiling with the posterior patch, the aortic prosthesis was secured to the aortic annulus and the pericardial patch. The anterior patch was used to close the right side of the aortotomy. The postoperative course was uneventful, and postoperative echocardiography revealed no paravalvular leakage.

BACKGROUND: Pedicled flaps are useful for reconstructive surgery. Previously, we often used vascularized supraclavicular flaps, especially for head and neck reconstruction, but then shifted to using thoracic branch of the supraclavicular artery (TBSA) flaps. However, limited research exists on the anatomy of TBSA flaps and on the use of indocyanine green (ICG) fluorescence videoangiography for supraclavicular artery flaps. We utilized ICG fluorescence videoangiography to harvest reliable flaps in reconstructive operations, and describe the results herein. METHODS: Data were retrospectively reviewed from six patients (five men and one woman: average age, 54 years; range, 48–60 years) for whom ICG videoangiography was performed to observe the skin perfusion of a supraclavicular flap after it was raised. Areas where the flap showed good enhancement were considered to be favorable for flap survival. The observation of ICG dye indicated good skin perfusion, which is predictive of flap survival; therefore, we trimmed any areas without dye filling and used the remaining viable part of the flap. RESULTS: The flaps ranged in size from 13×5.5 cm to 17×6.5 cm. One patient received a conventional supraclavicular flap, four patients received a TBSA flap, and one patient received a flap that was considered to be intermediate between a supraclavicular flap and a TBSA flap. The flaps completely survived in all cases, and no flap necrosis was observed. CONCLUSIONS: The TBSA flap is very useful in reconstructive surgery, and reliable flaps could be obtained by using ICG fluorescence videoangiography intraoperatively.
Arteries ; Female ; Fluorescence ; Head ; Humans ; Indocyanine Green ; Male ; Neck ; Necrosis ; Perfusion ; Reconstructive Surgical Procedures ; Retrospective Studies ; Skin ; Surgical Flaps

Treating a thoracic aortic aneurysm (TAA) after coronary artery bypass graft (CABG) surgery requires an appropriate surgical procedure to preserve the functional graft. We present a case of hybrid procedure of thoracic endovascular aortic repair combined with a redo off-pump CABG via median sternotomy. The patient was a 76-year-old man with a history of CABG and abdominal aortic replacement in a different country. Chest computed tomography revealed a saccular-shaped aortic aneurysm in the distal aortic arch with diameter of 5.6 cm. Coronary angiography revealed theLIMA graft was patent but anastomosed to the diagonal branch and the left anterior descending artery (LAD) was totally occluded and was opacified through the right coronary artery. Significant ischemic change in the anteroseptal wall suggested a requirement of surgical revascularization of LAD. The chest was opened via re-midsternotomy. Then the 3 arch vessels were reconstructed with a trifurcated artificial graft attached to the ascending aorta and coronary artery bypass grafting was performed on the beating heart. Finally, the aneurysm was excluded by introducing a stent graft through the graft to zone 0. The patient's postoperative course was uneventful and he was discharged on postoperative day 16. A hybrid procedure via median sternotomy was useful in the surgery for TAA with the functional LIMA after CABG.

Moderate to vigorous physical activity is associated with improving insulin resistance in overweight and obese adults. However, effect of light physical activity on insulin resistance remains to be fully elucidated. The purpose of this study was to investigate the effect of light physical activity on insulin resistance in overweight and obese men. Thirty-seven overweight and obese middle-aged men (28.9 ± 1.8 kg/m², 51.0 ± 8.8 years) participated in this study. They took part in the lifestyle intervention (calorie restricted diet and exercise) for 12 weeks. Anthropometric parameters, fasting glucose, HbA1c, fasting insulin, and HOMA-IR were assessed at baseline and post intervention. Physical activity was objectively measured using a triaxial accelerometer at baseline and during intervention. Light physical activity (+17.7 min/day) and moderate-vigorous physical activity (+33.2 min/day) increased significantly, while body weight (-12.4 kg), fasting glucose (-9.5 mg/ml), fasting insulin (-4.2 μU/ml), and HOMA-IR (-1.1) decreased significantly. The change in light physical activity from baseline to during intervention were inversely related to change in fasting insulin (r = 0.18, P = 0.02) and change in HOMA-IR (r = -0.16, P = 0.03), after adjustment for several confounders. These results suggest that an increase of light physical activity improves insulin resistance in overweight and obese men.

Animals ; Cellular Reprogramming ; Dentate Gyrus ; cytology ; Fibroblasts ; cytology ; Mice ; Neural Stem Cells ; cytology ; transplantation ; Swine