Effects of switching from a dipeptidyl peptidase-4 inhibitor to luseogliflozin on nocturnal blood pressure in patients with type 2 diabetes: protocol for a multicentre, prospective, randomised, open-label, blinded endpoint parallel-group comparison study.

Introduction: Nocturnal hypertension is clinically important for patients with type 2 diabetes (T2D), considering its strong correlation with cardiovascular events. We aim to test the hypothesis that the sodium-glucose cotransporter 2 inhibitor, luseogliflozin, ameliorates nocturnal hypertension more effectively than a dipeptidyl peptidase (DPP)-4 inhibitor in patients with T2D.

Methods And Analysis: This study is a multicentre, prospective, randomised, open-label, blinded endpoint parallel-group trial.

Rotational thromboelastometry-guided perioperative management of coagulation in a patient with Heyde's syndrome undergoing transcatheter aortic valve implantation.

Background: Changes in coagulability during the hyperacute phase within 24 h after transcatheter aortic valve implantation (TAVI) for Heyde's syndrome, or aortic stenosis complicated by gastrointestinal angiodysplasia and acquired coagulation dysfunction, have not been clarified. We evaluated perioperative changes in coagulability using rotational thromboelastometry (ROTEM).

Case Presentation: A female patient with Heyde's syndrome in her 80s underwent TAVI.

[CD20-negative diffuse large B-cell lymphoma complicated by rheumatoid arthritis].

CD20 antigen is an important marker for diagnosis of B-cell neoplasms that is highly expressed on the surface of neoplastic B lymphocytes. Patients with rheumatoid arthritis (RA) have an increased risk of developing malignant lymphoma, of which diffuse large B-cell lymphoma (DLBCL) is the most common type. We report an unusual case of CD20-negative DLBCL complicated by rheumatoid arthritis.

Branched-chain amino acids-induced cardiac protection against ischemia/reperfusion injury.

Aims: Amino acids, especially branched chain amino acids (BCAAs), have important regulatory roles in protein synthesis. Recently studies revealed that BCAAs protect against ischemia/reperfusion (I/R) injury. We studied the signaling pathway and mitochondrial function affecting a cardiac preconditioning of BCAAs.

Correlation between serum proinsulin levels and fatty liver: The Dynamics of Lifestyle and Neighborhood Community on Health Study.

Aims/introduction: We explored the association between fatty liver and pancreatic β-cell dysfunction in a general population.

Materials And Methods: This cross-sectional study included 489 (53.8% women) community-dwelling Japanese adults.

Oversized ubiquinones as molecular probes for structural dynamics of the ubiquinone reaction site in mitochondrial respiratory complex I.

NADH-quinone oxidoreductase (complex I) couples electron transfer from NADH to quinone with proton translocation across the membrane. Quinone reduction is a key step for energy transmission from the site of quinone reduction to the remotely located proton-pumping machinery of the enzyme. Although structural biology studies have proposed the existence of a long and narrow quinone-access channel, the physiological relevance of this channel remains debatable.

Impact of sodium-glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria.

Background: We compared the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria.

Methods: A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m) was conducted.

Eye-gaze information input based on pupillary response to visual stimulus with luminance modulation.

This study develops an information-input interface in which a visual stimulus targeted by a user's eye gaze is identified based on the pupillary light reflex to periodic luminance modulations of the object. Experiment 1 examines how pupil size changes in response to periodic luminance modulation of visual stimuli, and the results are used to develop an algorithm for information input. Experiment 2a examines the effectiveness of interfaces with two objects.

Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis.

Chronic inflammation is accompanied by recurring cycles of tissue destruction and repair and is associated with an increased risk of cancer. However, how such cycles affect the clonal composition of tissues, particularly in terms of cancer development, remains unknown. Here we show that in patients with ulcerative colitis, the inflamed intestine undergoes widespread remodelling by pervasive clones, many of which are positively selected by acquiring mutations that commonly involve the NFKBIZ, TRAF3IP2, ZC3H12A, PIGR and HNRNPF genes and are implicated in the downregulation of IL-17 and other pro-inflammatory signals.

Switching to Once-Daily Insulin Degludec/Insulin Aspart from Basal Insulin Improves Postprandial Glycemia in Patients with Type 2 Diabetes Mellitus: Randomized Controlled Trial.

Background: To explore the efficacy and safety of switching from once-daily basal insulin therapy to once-daily pre-meal injection insulin degludec/insulin aspart (IDegAsp) with respect to the glycemic control of participants with type 2 diabetes mellitus (T2DM).

Methods: In this multicenter, open-label, prospective, randomized, parallel-group comparison trial, participants on basal insulin therapy were switched to IDegAsp (IDegAsp group; =30) or continued basal insulin (Basal group; =29). The primary endpoint was the superiority of IDegAsp in causing changes in the daily blood glucose profile, especially post-prandial blood glucose concentration after 12 weeks.

Relationships between plasma lactate, plasma alanine, genetic variations in lactate transporters and type 2 diabetes in the Japanese population.

The present study aimed to characterize the relationships between plasma lactate, plasma alanine, monocarboxylate transporter (MCT) polymorphisms, and indices of diabetes in patients with type 2 diabetes (T2D) in Japan. Eighty-three patients with T2D were prospectively enrolled. The gluconeogenesis and glycogenolysis are enhanced and uptake of glucose is decreased in the T2D liver.

Neuroendocrine carcinoma diagnosis from bile duct cytological specimens: A retrospective single-center study.

Neuroendocrine carcinoma (NEC) in the extrahepatic bile duct is extremely rare and clinically aggressive. Cytological examination of bile and/or bile duct brushing specimens plays an important role in the diagnosis of carcinoma of the extrahepatic bile duct, but only a few articles have described the cytological features of NEC in this area. Thus, we retrospectively analyzed the cytological features of NEC in bile and/or bile duct brushing specimens.

Active site rearrangement and structural divergence in prokaryotic respiratory oxidases.

Cytochrome bd-type quinol oxidases catalyze the reduction of molecular oxygen to water in the respiratory chain of many human-pathogenic bacteria. They are structurally unrelated to mitochondrial cytochrome c oxidases and are therefore a prime target for the development of antimicrobial drugs. We determined the structure of the cytochrome bd-I oxidase by single-particle cryo-electron microscopy to a resolution of 2.

Favourable effect of the sodium-glucose co-transporter-2 inhibitor canagliflozin plus the dipeptidyl peptidase-4 inhibitor teneligliptin in combination on glycaemic fluctuation: An open-label, prospective, randomized, parallel-group comparison trial (the CALMER study).

This multicentre, prospective, randomized, open-label, blinded-endpoint, parallel-group, short-term (4-5 weeks) controlled trial was conducted to investigate the superiority of the effect of reducing mean amplitude of glycaemic excursions (MAGE) during meal tolerance tests (MTTs) for the combination of dipeptidyl peptidase-4 (DPP-4) inhibitor and sodium-glucose co-transporter-2 (SGLT2) inhibitor compared with SGLT2 inhibitor monotherapy. Ninety-nine patients with type 2 diabetes who were taking teneligliptin (20 mg/d) were randomized to one of the following two groups: those who switched to 100 mg/d of canagliflozin (SWITCH group) or those who added 100 mg/d of canagliflozin (COMB group). MAGE in the COMB group was significantly decreased compared with that in the SWITCH group (COMB 117.

[Clinical features of adult-onset chronic active Epstein-Barr virus infection].

Chronic active Epstein-Barr virus infection (CAEBV) presents with mononucleosis-like symptoms such as chronic persistent or recurrent pyrexia, lymphadenopathy, and hepatosplenomegaly because of the reactivation of Epstein-Barr virus (EBV) as demonstrated by the recurrence of EBV-infected cells. The mechanism of CAEBV remains obscure, and CAEBV can lead to fatal conditions such as hemophagocytic syndrome and malignant lymphoma by clonal expansion of EBV-infected T- or NK-cells. Without hematopoietic stem cell transplantation, CAEBV has a poor prognosis.

Photoaffinity Labeling of Respiratory Complex I in Bovine Heart Submitochondrial Particles by Photoreactive [I] amilorides.

The architecture of quinone/inhibitor-access channel in proton-translocating NADH-quinone oxidoreductase (respiratory complex I) was modeled by X-ray crystallography and cryo-EM, however, it remains debatable whether the channel model reflects the physiologically relevant state present throughout the catalytic cycle. Using photoreactive [I]amilorides, we demonstrated that amiloride-type inhibitors bind to the interfacial region of multiple subunits (49-kDa, ND1, PSST, and 39-kDa subunits), which is difficult to reconcile with the current channel model. This report describes the procedures for photoaffinity labeling of bovine submitochondrial particles by photoreactive [I]amilorides.

Gitelman's syndrome with hyperphosphatemia, effectively responding to single oral magnesium oxide administration: A case report.

Rationale: The Gitelman's syndrome (GS) is characterized by metabolic alkalosis, hypokalemia, hypomagnesemia, and hypocalciuria. However, the involvement of this deranged electrolyte balance in patients with GS in parathyroid hormone action has not been known.

Patient Concerns: We report a 34-year-old woman with muscle weakness and tetany/seizures caused by electrolyte imbalance.

Cross-cultural adaptation of the Chronic Illness Resources Survey in Japanese patients with diabetes.

Aim: The Chronic Illness Resources Survey (CIRS) is a tool for assessing multiple levels of resources for self-management in people with chronic illnesses. This study aimed to examine the reliability and validity of the Japanese version of the CIRS (CIRS-J) among patients with diabetes.

Methods: This study included 102 Japanese patients with diabetes.

Factors with remission of fatty liver in patients with type 2 diabetes treated with ipragliflozin.

We investigated the factors associated with fatty liver remission via treatment with ipragliflozin. The analysis was obtained from our multi-center prospective observational study, including 200 Japanese patients with type 2 diabetes treated with ipragliflozin (50 mg/day) for 24 weeks. The extent of fatty liver was estimated using a fatty liver index (FLI).

Recent innovations in therapeutic endoscopy for pancreatobiliary diseases.

The development of endoscopic treatment for pancreatobiliary diseases in recent years is remarkable. In addition to conventional transpapillary treatments under endoscopic retrograde cholangiopancreatography (ERCP), new endoscopic ultrasound-guided therapy is being developed and implemented. On the other hand, due to the development/improvement of various devices such as new metal stents, a new therapeutic strategy under ERCP is also advocated.

Discovery of a pyrazolo[1,5-a]pyrimidine derivative (MT-3014) as a highly selective PDE10A inhibitor via core structure transformation from the stilbene moiety.

We have developed a new class of PDE10A inhibitor, a pyrazolo[1,5-a]pyrimidine derivative MT-3014 (1). A previous compound introduced was deprioritized due to concerns for E/Z-isomerization and glutathione-adduct formation at the core stilbene structure. We discovered pyrazolo [1,5-a] pyrimidine as a new lead scaffold by structure-based drug design utilizing a co-crystal structure with PDE10A.