Targeting senescent cells for the treatment of age-associated diseases.

Cellular senescence, which entails cellular dysfunction and inflammatory factor release-the senescence-associated secretory phenotype (SASP)-is a key contributor to multiple disorders, diseases, and the geriatric syndromes. Targeting senescent cells using senolytics has emerged as a promising therapeutic strategy for these conditions. Among senolytics, the combination of dasatinib and quercetin (D + Q) was the earliest and one of the most successful so far.

Additional benefits of belimumab in chronic phase of systemic lupus erythematosus and efficacy of tacrolimus combination therapy.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease; although severe disease and refractoriness to existing therapies are still experienced, the number of cases resistant to remission induction has decreased with the establishment of various therapies. However, improving long-term prognosis remains a challenge due to the unavoidable prolonged use of non-selective glucocorticoids. To investigate the additional effect of belimumab in the chronic phase, we included 28 of 46 patients with SLE who were initiated on belimumab between January 2018 and October 2022 for glucocorticoid reduction.

The role of sonic hedgehog signaling in the oropharyngeal epithelium during jaw development.

Sonic hedgehog (Shh) is expressed in the oropharyngeal epithelium, including the frontonasal ectodermal zone (FEZ), which is defined as the boundary between Shh and Fgf8 expression domains in the frontonasal epithelium. To investigate the role of SHH signaling from the oropharyngeal epithelium, we generated mice in which Shh expression is specifically deleted in the oropharyngeal epithelium (Isl1-Cre; Shh). In the mutant mouse, Shh expression was excised in the oropharyngeal epithelium as well as FEZ and ventral forebrain, consistent with the expression pattern of Isl1.

Decoding Brain Development and Aging: Pioneering Insights From MRI Techniques.

The aging process induces a variety of changes in the brain detectable by magnetic resonance imaging (MRI). These changes include alterations in brain volume, fluid-attenuated inversion recovery (FLAIR) white matter hyperintense lesions, and variations in tissue properties such as relaxivity, myelin, iron content, neurite density, and other microstructures. Each MRI technique offers unique insights into the structural and compositional changes occurring in the brain due to normal aging or neurodegenerative diseases.

Cost-effectiveness of ferric citrate hydrate in patients with iron deficiency anemia.

We investigated the cost-effectiveness of treating iron deficiency anemia (IDA) with ferric citrate hydrate (FC) in Japan. We employed four treatment strategies: switching from sodium ferrous citrate (SF) to FC at (1) 500 mg (approximately 120 mg of iron) per day or (2) 1000 mg (approximately 240 mg of iron) per day in patients with SF-induced nausea/vomiting, or starting treatment with FC at (3) 500 mg/day or (4) 1000 mg/day. We evaluated the cost-effectiveness of these strategies compared with SF 100 mg (100 mg of iron) per day.

Urinary fatty acid-binding protein 4 is a promising biomarker for glomerular damage in patients with diabetes mellitus.

Aims/introduction: Fatty acid-binding protein (FABP) 4, which acts as an adipokine secreted by adipocytes, macrophages, and capillary endothelial cells, is expressed in injured glomerular cells. It has been reported that urinary (U-) FABP4 is associated with renal dysfunction and proteinuria in several glomerular kidney diseases. However, the clinical significance of U-FABP4 in diabetic kidney disease (DKD) remains undetermined.

Gastrointestinal symptoms in patients receiving imeglimin in combination with metformin: A post-hoc analysis of imeglimin clinical trial data.

Introduction: An increased rate of gastrointestinal (GI) symptoms is reported in patients with type 2 diabetes receiving imeglimin plus metformin vs monotherapy or in combination with other antidiabetic drugs. This post-hoc analysis explored GI symptom incidence, risk factors for their occurrence, and the impact on therapeutic efficacy during imeglimin and metformin combination therapy.

Materials And Methods: Data were derived from the 52-week, open-label, phase 3 TIMES-2 trial in Japanese type 2 diabetes patients.

Atherogenic Dyslipidemia Is Critically Related to Aortic Complicated Lesions in Cryptogenic Stroke.

Aims: Atherogenic dyslipidemia (AD) is regarded as a residual risk of cardiovascular diseases characterized by low high-density lipoprotein cholesterol (HDL-C) and high triglyceride (TG) levels and related to the intracranial stenosis of atheromatous thrombotic brain infarction (ATBI). Further, atherosclerosis is possibly related to another stroke subtype, including cryptogenic stroke (CS). In particular, an aortic complicated lesion (ACL) is a notable embolic source of CS, since recurrence of aortogenic brain embolism is not rare.

Design of buffer property for the new enrichment method of circulating tumor cell based on immunomagnetic-negative separation.

Metastasis is a significant contributor to cancer-related mortality and a critical issue in cancer. Monitoring the changes in circulating tumor cells (CTCs) with metastatic potential is a valuable prognostic and predictive biomarker. CTCs are a rare population in the peripheral blood of patients with cancer.

Association Between Sleep Duration and Cardiovascular Disease Among Asian Americans.

Background: Cardiovascular disease (CVD) prevalence varies widely among Asian American adults. The American Heart Association added healthy sleep to its metrics to define ideal cardiovascular health. Little is known about the association between sleep and CVD prevalence among Asian subgroups.

The relationship between long COVID, labor productivity, and socioeconomic losses in Japan: A cohort study.

Objectives: We examined shifts in labor productivity and their economic ramifications among adult patients with long COVID in Japan.

Methods: A total of 396 patients were categorized into three groups based on symptom progression: non-long COVID, long COVID recovered, and long COVID persistent. Patient-reported outcomes were assessed at three time intervals: 3, 6, and 12 months after COVID-19 diagnosis.

Successful Bailout of Catheter-Induced Dissection in Acute Myocardial Infarction Resulting From a Nondominant Right Coronary Artery Occlusion.

A 48-year-old male with a history of hyperlipidemia presented to the emergency department with chest pain. Electrocardiographic abnormalities indicated an acute coronary syndrome. Urgent coronary angiography revealed nondominant right coronary artery (RCA) occlusion.

Glucocorticoid tapering pace in microscopic polyangiitis and granulomatosis with polyangiitis in Japanese real-world practice: A propensity score-matched retrospective cohort study from the J-CANVAS registry.

Objective: To assess the prevalence and outcomes among regimens of glucocorticoid tapering for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) in real-world practice.

Methods: We retrospectively examined the Japan Collaborative Registry of ANCA-associated Vasculitis (J-CANVAS) registry, and evaluated the prevalence of glucocorticoid tapering regimens in the PEXIVAS trial. In patients with newly diagnosed MPA and GPA, we compared outcomes among standard and reduced pace regimens.

The transition of the criteria for disseminated intravascular coagulation and the targeted patients in randomized controlled trials over the decades: a scoping review.

Background: Disseminated intravascular coagulation (DIC) is a severe complication in septic patients. The Japanese Ministry of Health and Welfare (JMHW)-DIC criteria, the first DIC criteria, were established in 1983, and several other criteria have been proposed since then, including the International Society on Thrombosis and Haemostasis (ISTH)-overt DIC criteria and the Japanese Association for Acute Medicine (JAAM) DIC criteria. This study aimed to look into the transition of DIC criteria used in randomized controlled trials (RCTs) for sepsis-induced DIC.

Elucidation of the clinical traits of diabetic chorea through a questionnaire survey of people with diabetic chorea from 59 Japanese hospitals.

Aims: Diabetic chorea refers to sudden involuntary movements developing in people with diabetes mellitus and is known to occur mainly in those with severe hyperglycemia. We conducted a questionnaire survey of case-reporting facilities in Japan to elucidate their clinical characteristics.

Methods: We searched the PubMed and Ichushi databases for case reports published from January 1, 2012, to December 31, 2017, using "diabetes" and "chorea" as keywords, and sent a questionnaire to the reporting institutions.

Efficacy and Safety of Sodium Zirconium Cyclosilicate in the Management of Hyperkalemia in Patients with Heart Failure with Reduced and Mildly Reduced Ejection Fraction and Chronic Kidney Disease Treated with Spironolactone: Rationale for and Design of the REGISTA-K Trial.

Background: To evaluate whether sodium zirconium cyclosilicate (SZC) enables the up-titration of spironolactone without increasing the risk of hyper- and hypokalemia in patients with heart failure with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) and moderate/severe chronic kidney disease (CKD) who developed hyperkalemia during treatment with suboptimal spironolactone dose.

Methods: The REGISTA-K is a randomized, double-blind, placebo-controlled, multicenter trial that examined the efficacy and safety of SZC in up-titrating spironolactone without the occurrence of hyperkalemia or hypokalemia. A total of 266 patients with HFrEF and HFmrEF and hyperkalemia will be randomized in a 1:1 ratio to receive either SZC or placebo after treating hyperkalemia with SZC at 25 sites in Japan.

Dantrolene inhibition of ryanodine receptor 1 carrying the severe malignant hyperthermia mutation Y522S visualized by cryo-EM.

Mutations in the skeletal isoform of the ryanodine receptor 1 (RyR1) pose grave risks during anesthesia or treatment with succinylcholine muscle relaxants. These can trigger a potentially lethal malignant hyperthermia (MH) episode via intracellular calcium increase mainly from RyR1 channel leakage. Dantrolene is the only known treatment option to prevent death.

Evidence-based diagnostic prediction score for pediatric NMDA receptor encephalitis.

Objective: Early diagnosis and treatment of anti-N-methyl-D-aspartate receptor encephalitis (NMDARE) are crucial for a favorable prognosis. Detecting the causative autoantibodies can be challenging. Probable diagnostic criteria are useful in adults less so in children.

Randomized, multicenter, active-controlled open-label study of NPC-25, zinc histidine hydrate, (non-inferiority to NOBELZIN™, zinc acetate dihydrate) for patients with hypozincemia.

Objective: This study evaluated the efficacy and safety of NPC-25, zinc histidine hydrate, in patients with hypozincemia. This randomized multicenter active-controlled open-label trial aimed to verify the non-inferiority of NPC-25 to NOBELZIN™, zinc acetate dihydrate.

Methods: Participants whose serum zinc concentrations were <70 μg/dL at two points within 8 weeks before the start of treatment were randomized 1:1 into the NPC-25 (active drug) administration group and the NOBELZIN™ (control drug) administration group, using dynamic allocation.

Investigation of predictors of latent visual impairment in patients with sellar lesions.

Objective: Patients with sellar lesions compressing the optic nerve sometimes perceive visual improvement after lesion resection, despite the absence of visual impairment on preoperative ophthalmological examination. This study investigated the indicators of latent visual impairment in patients with sellar lesions.

Methods: Forty-five patients who underwent surgery for sellar lesions compressing the optic nerve with no preoperative visual abnormalities and no change in visual assessment between pre- and postoperative ophthalmological examinations were divided into two groups: 1) patients who perceived recovery of visual function after lesion resection (the improved group), and 2) patients who did not (the unaffected group).

Preventable diagnostic errors of lower gastrointestinal perforation: a secondary analysis of a large-scale multicenter retrospective study.

Background: Lower gastrointestinal perforation (LGP) is an acute abdominal condition associated with a high mortality rate. Timely and accurate diagnosis is crucial. Nevertheless, a diagnostic delay has been estimated to occur in approximately one-third of the cases, and the factors contributing to this delay are yet to be clearly understood.