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.

We present the case of a 76-year-old man who underwent preoperative endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for obstructive jaundice caused by pancreatic head cancer. The patient had obstructive jaundice and cholangitis during neoadjuvant chemotherapy. Transpapillary biliary drainage using endoscopic retrograde cholangiopancreatography was attempted; however, it was unsuccessful because of duodenal tumor invasion. Therefore, EUS-HGS was performed. Jaundice and cholangitis improved promptly after EUS-HGS, and stent obstruction and migration were not observed before surgery. The stent was safely removed during surgery, and no postoperative complications occurred. Most studies of EUS-HGS for preoperative biliary drainage have been small and retrospective, and few have examined the safety of intraoperative stent removal. The fistula in our patient was promptly identified and the stent was safely removed despite the relatively limited field of view during robot-assisted laparoscopy.The promising findings of our case report can be used to inform EUS-based surgical strategies for biliary drainage with obstructive jaundice.

We present the case of a 76-year-old man who underwent preoperative endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for obstructive jaundice caused by pancreatic head cancer. The patient had obstructive jaundice and cholangitis during neoadjuvant chemotherapy. Transpapillary biliary drainage using endoscopic retrograde cholangiopancreatography was attempted; however, it was unsuccessful because of duodenal tumor invasion. Therefore, EUS-HGS was performed. Jaundice and cholangitis improved promptly after EUS-HGS, and stent obstruction and migration were not observed before surgery. The stent was safely removed during surgery, and no postoperative complications occurred. Most studies of EUS-HGS for preoperative biliary drainage have been small and retrospective, and few have examined the safety of intraoperative stent removal. The fistula in our patient was promptly identified and the stent was safely removed despite the relatively limited field of view during robot-assisted laparoscopy.The promising findings of our case report can be used to inform EUS-based surgical strategies for biliary drainage with obstructive jaundice.

We present the case of a 76-year-old man who underwent preoperative endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) for obstructive jaundice caused by pancreatic head cancer. The patient had obstructive jaundice and cholangitis during neoadjuvant chemotherapy. Transpapillary biliary drainage using endoscopic retrograde cholangiopancreatography was attempted; however, it was unsuccessful because of duodenal tumor invasion. Therefore, EUS-HGS was performed. Jaundice and cholangitis improved promptly after EUS-HGS, and stent obstruction and migration were not observed before surgery. The stent was safely removed during surgery, and no postoperative complications occurred. Most studies of EUS-HGS for preoperative biliary drainage have been small and retrospective, and few have examined the safety of intraoperative stent removal. The fistula in our patient was promptly identified and the stent was safely removed despite the relatively limited field of view during robot-assisted laparoscopy.The promising findings of our case report can be used to inform EUS-based surgical strategies for biliary drainage with obstructive jaundice.

Objective: In the treatment of patients with schizophrenia, pro re nata (PRN) drugs are commonly prescribed for medical indications such as agitation, acute psychiatric symptoms, insomnia, and anxiety. However, high-quality evidence supporting the use of PRN medications is lacking, and these drugs are administered on the basis of clinical experience and habits. Therefore, the actual use of psychotropic PRN drugs and its influence on the patients’ outcomes need to be investigated. Methods: This study included 205 patients who underwent inpatient treatment for schizophrenia. We investigated the prescription of psychotropic drugs before admission and at discharge, as well as the dosing frequency of PRN drugs during hospitalization. We also examined the influence of psychotropic PRN drug use on hospitalization days, antipsychotic polypharmacy, and readmission rates. Results: Patients who used psychotropic PRN drugs during hospitalization had significantly longer hospitalization days (p = 7.5 × 10−4 ) and significantly higher rates of antipsychotic polypharmacy (p = 2.4 × 10−4 ) at discharge than those who did not use psychotropic PRN drugs. Moreover, a higher number of psychotropic PRN drugs used per day was associated with higher readmission rates within 3 months of discharge (p = 4.4 × 10−3 ). Conclusion Psychotropic PRN drug use is associated with prolonged hospitalization, antipsychotic polypharmacy, and increased readmission rates in inpatients with schizophrenia. Therefore, psychiatric symptoms should be stabilized with regularly prescribed medications without the extensive use of psychotropic PRN drugs. Moreover, a system for monitoring and reexamining PRN drug use needs to be established.

Glycosylation of the Fc region of IgG has a profound impact on the safety and clinical efficacy of therapeutic antibodies. While the biantennary complex-type oligosaccharide attached to Asn297 of the Fc is essential for antibody effector functions, fucose and outer-arm sugars attached to the core heptasaccharide that generate structural heterogeneity (glycoforms) exhibit unique biological activities. Hence, efficient and quantitative glycan analysis techniques have been increasingly important for the development and quality control of therapeutic antibodies, and glycan profiles of the Fc are recognized as critical quality attributes. In the past decade our understanding of the influence of glycosylation on the structure/function of IgG-Fc has grown rapidly through X-ray crystallographic and nuclear magnetic resonance studies, which provides possibilities for the design of novel antibody therapeutics. Furthermore, the chemoenzymatic glycoengineering approach using endoglycosidase-based glycosynthases may facilitate the development of homogeneous IgG glycoforms with desirable functionality as next-generation therapeutic antibodies. Thus, the Fc glycans are fertile ground for the improvement of the safety, functionality, and efficacy of therapeutic IgG antibodies in the era of precision medicine.
Animals ; Antibodies, Monoclonal ; adverse effects ; pharmacokinetics ; therapeutic use ; Glycosylation ; Humans ; Immunoglobulin G ; chemistry ; metabolism ; Protein Engineering ; methods ; Receptors, Fc ; chemistry ; metabolism ; Treatment Outcome