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.

While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), the underlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, including heart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment by periodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate the relationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes (NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagy inhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. This study also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomal sensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity than gingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wild-type P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-type P.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which are virulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms the strong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.
Mice ; Rats ; Animals ; Porphyromonas gingivalis ; Gingipain Cysteine Endopeptidases ; Autophagosomes ; Myocardium ; Periodontal Diseases ; Heart Rupture

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.

Objectives : Many reports have investigated the work environment of physicians and reported the association between work environment, burnout, and the quality of medical care. We aimed to determine the key to improving the work environment by analyzing the results of a Japanese survey for young cardiovascular surgeons. Methods : A survey on work environment was performed among the young members of The Japanese Society for Cardiovascular Surgery (≤40 years of age) to measure their job satisfaction for 9 items : operation, perioperative work, number of hours working or sleeping, board affairs (application or renewal of board certification), motivation, salary, days off, quality of life, and mental status. Univariate and multivariate analyses using 16 factors for the work environment (age, number of years in practice, gender, subspecialty, board certification in surgery, board certification in cardiovascular surgery, primary practice hospital, workdays and nights on duty in a primary practice setting, workdays and nights on duty outside primary practice, total annual income, overtime work hours, overtime entitlement, gap in overtime work and entitlement, and presence of an intensive care unit [ICU] managed by ICU physicians) were performed to identify the risk factors for dissatisfaction. Results : The survey was completed by 327 of 1,304 (25.1% response rate) young members of the Japanese Society for Cardiovascular Surgery. The respondents had an average of 8.5±3.5 years in practice, and 292 (89.3%) respondents were male. Only 14.2% of the responding young surgeons reported no dissatisfaction in any items. In all items, the young surgeons were most satisfied with operation (34.6% of all responders). Age, years in practice, female gender, board certification in surgery, working at a university hospital, workdays in a primary practice setting, and workdays outside a primary practice setting were identified as significant factors for dissatisfaction, while a subspecialty in vascular surgery, total annual income, board certification in cardiovascular surgery, and the presence of an ICU managed by ICU physicians were identified as significant factors against dissatisfaction in the work environment. Conclusions : Our analyses of the survey results identified a number of risk factors for dissatisfaction in the work environment among young cardiovascular surgeons. Regarding the quality of medical care, respondents hoped for a reduced burden on surgeons and the establishment of a work-shift system in the cardiovascular department and an interdisciplinary team including an ICU physician. Multidimensional analyses including job satisfaction, rewards as training, and a quantitative evaluation of the quality of medical care will be necessary to clarify the corresponding relationship between consumers and providers of cardiovascular surgery in the work environment.

A 58-year-old man who complained of dyspnea on effort was given a diagnosis of decompensated congestive heart failure. Echocardiography revealed severe aortic regurgitation and cardiomegaly. We decided to perform aortic valve replacement with a mechanical valve, however his past history made us suspicious of allergy to metal. From his previous patient records, we determined he was allergic to many metals : gold, iron, platinum, cobalt, chrome, bronze, and zinc. Newly performed skin patch tests showed positive reactions to aluminum, tin, palladium, indium, iridium and stainless steel. We selected a CarboMedics mechanical valve made of nickel-titanium alloy. Aortic valve replacement with a 27-mm CarboMedics mechanical valve was performed by median sternotomy. At sternum closure, we used polyester non-absorbable suture thread, instead of surgical steel wire, because it contains stainless steel. His postoperative progress was good and he was discharged on the 10th postoperative day. One year after surgery he is doing well without any allergic symptoms.

A 25-year-old man with a previous diagnosis of congenital bicuspid aortic valve presented with a fever of unknown origin for 3 months. Transthoracic echocardiography revealed vegetation on the mitral valve leaflet. Transesohageal echocardiography revealed severe aortic regurgitation and a mitral valve leaflet aneurysm. Despite intensive antibiotic therapy, his clinical condition did not improve, so he underwent aortic and mitral valve repair. The aortic valve was shown to be unicuspid intraoperatively. We made a new commissure, then mitral valve aneurysm was resected and a new leaflet was made using the pericardium. There was almost no regurgitation seen on postoperative echocardiography.

Non-occlusive mesenteric ischemia (NOMI) is a rare but often fatal event following cardiac surgery. Early diagnosis of NOMI is difficult because the related abdominal symptoms are not very specific. From April 1999 to September 2003, 1,040 patients underwent cardiac surgery, among whom 5 patients who underwent angiography were given a diagnosis of NOMI. A catheter was used for immediate intra-arterial infusion of 500μg prostaglandin E1 into the superior mesenteric artery over a period of 30min. Prior to angiography, all patients had cutis marmorata and elevated serum lactate levels. Three patients showed peritoneal signs and therefore underwent laparotomy. Of the 5 patients, 4 survived. In conclusion, if mesenteric ischemia is suspected, selective angiography must be performed as soon as possible for diagnosis and treatment. Additionally, the presence of other findings such as cutis marmorata and elevated serum lactate levels proved to be useful in the early diagnosis of NOMI.