Establishment of a method to measure the intracellular potassium ion concentration of brain tissue using a simple device.

Intracellular potassium ion (K) concentration is higher than extracellular K concentration. Some cells maintain intracellular potassium levels by taking up extracellular potassium. However, investigating these details requires techniques to measure intracellular potassium concentrations.

Roxadustat-Induced Central Hypothyroidism in Renal Anemia Patients: Insights From Antineutrophil Cytoplasmic Antibody-Related Vasculitis Cases.

The introduction of hypoxia-inducible factor-prolyl hydroxylase (HIF-PH) inhibitors in Japan in 2019 for treating renal anemia in hemodialysis patients has resulted in an adverse event: central hypothyroidism. Although this adverse event was not widely recognized by the public, it was first documented in Japan in 2021. Despite limited case reports on roxadustat, an oral HIF-PH inhibitor that induces central hypothyroidism, this condition typically improves rapidly upon discontinuation of the drug.

A Case of Rhabdomyolysis Induced by Antipsychotic Medication With Creatine Kinase (CK) Levels Elevated to 420,000 U/L, Resulting in Acute Kidney Injury (AKI) and Necessitating Hemodialysis.

A 45-year-old man on public welfare, who had been visiting a psychiatric hospital for schizoaffective disorder, began working as a package delivery person for the first time in the morning after receiving welfare. In the afternoon, he noticed pain in his lower back. By evening, he was unable to move, prompting an emergency call and transportation to our hospital.

Long-lasting increases in GABA receptor subunit levels in hippocampal dentate gyrus of mice with a single systemic injection of trimethyltin.

We have recently shown delayed increases in GABA receptor (GABAR) subunit protein levels in the hippocampal dentate gyrus (DG), but not in the pyramidal CA1 and CA3 regions, at 15-30 days after the systemic single administration of trimethyltin (TMT) in mice. An attempt was thus made to determine whether the delayed increases return to the control levels found in naive mice afterward. In the DG on hippocampal slices obtained at 90 days after the administration, however, marked increases were still seen in protein levels of both GABAR1 and GABAR2 subunits without significant changes in calbindin and glial fibrillary acidic protein (GFAP) levels on immunoblotting analysis.

Post-translational modifications of the apelin receptor regulate its functional expression.

Post-translational modifications (PTMs) are protein modifications that occur after protein biosynthesis, playing a crucial role in regulating protein function. They are involved in the functional expression of G-protein-coupled receptors (GPCRs), as well as intracellular and secretory protein signaling. Here, we aimed to investigate the PTMs of the apelin receptor (APLNR), a GPCR and their potential influence on the receptor's function.

Trajectory for the Regulatory Approval of a Combination of Pertuzumab Plus Trastuzumab for Pre-treated HER2-positive Metastatic Colorectal Cancer Using Real-world Data.

Utilizing real-world data (RWD) for effective clinical implementation is becoming more and more appealing as the cost of drug development rises, especially for patients with rare diseases and rare molecular subtypes for whom conducting randomized controlled trials is challenging. If a regulatory approval methodology based on RWD as an external control group can be established, drug development for rarer fractions can be accelerated by lowering costs and time, as well as reducing physical and emotional burdens on both patients and healthcare professionals. Since 2017, we have been prospectively collecting the clinical data of standard therapies in patients with rare molecular fractions under the SCRUM-Japan Registry platform, which is a qualified registry utilized as external control data for regulatory submission.

Delayed Expression of Both GABAR1 and GABAR2 Subunits in Murine Hippocampal Dentate Gyrus After a Single Systemic Injection of Trimethyltin.

Trimethyltin (TMT) has been used as a cytotoxin to neurons rather than glial cells in the mammalian hippocampus. The systemic administration of TMT led to declined fluorescence of ZnAF-2 DA staining as a marker of intact mossy fibers and increased fluorescence of Fluoro-Jade B staining as a marker of degenerated neurons during the initial 2 to 5 days after the administration with later ameliorations within 30 days in the hippocampal dentate gyrus (DG) and CA3 region in mice. On immunoblotting analysis, both GABAR1 and GABAR2 subunit levels increased during 15 to 30 days after TMT along with significant decreases in glutamatergic GluA1 and GluA2/3 receptor subunit levels during 2 to 7 days in the DG, but not in other hippocampal regions such as CA1 and CA3 regions.

Secondary Adrenal Insufficiency After COVID-19 Diagnosed by Insulin Tolerance Test and Corticotropin-Releasing Hormone Test.

Coronavirus disease 2019 (COVID-19) can affect multiple organs and systems, including the endocrine system. Its symptoms can last for months, resulting in post-COVID-19 conditions, among others. A small number of patients have central adrenal insufficiency (CAI) months after recovery from COVID-19; nevertheless, its pathogenesis has not been fully elucidated.

Autoantibody profiles associated with morbidity and mortality in scleroderma renal crisis.

Objective: The aim of this study was to investigate association of autoantibodies with scleroderma renal crisis (SRC) among Japanese patients.

Methods: The clinical characteristics and mortality of 330 patients with sytemic screlosis (SSc) at Kyoto University Hospital were retrospectively analysed, focusing on possible association with anti-topoisomerase I (anti-topo I), anti-centromere (ACA), anti-RNA polymerase III (RNAPIII) and/or anti-U1-RNP. Logistic regression analyses were performed to reveal any association of these autoantibodies with the development and mortality of SRC.

Stabilometric analysis of neck orientations during mealtime by a wearable device for dysphagia patients.

Postural changes are commonly used treatment to prevent the elderly from the risk of aspiration pneumonia. However, the evidence-based studies regarding effectiveness of this treatment remains unclear since no systematic method exists to measure constantly changing postures without disturbing usual eating behaviors. In this paper, using IMU system attached to a smart-phone based wearable technology, we analyzed data of the neck orientation angles obtained from the dysphagia patients and healthy adults during their mealtime and attempted to see if the obtained data can show differences regarding the dynamics of the angles.

Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial.

The applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 (HER2) amplification prospectively confirmed by tumor tissue or ctDNA analysis ( UMIN000027887 ). HER2 amplification was confirmed in tissue and/or ctDNA in 30 patients with mCRC.

Resistance of SARS-CoV-2 variants to neutralization by antibodies induced in convalescent patients with COVID-19.

Administration of convalescent plasma or neutralizing monoclonal antibodies (mAbs) is a potent therapeutic option for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, SARS-CoV-2 variants with mutations in the spike protein have emerged in many countries. To evaluate the efficacy of neutralizing antibodies induced in convalescent patients against emerging variants, we isolate anti-spike mAbs from two convalescent COVID-19 patients infected with prototypic SARS-CoV-2 by single-cell sorting of immunoglobulin-G-positive (IgG) memory B cells.

Clinicopathological characteristics of lymphoproliferative disorders in 232 patients with rheumatoid arthritis in Japan: A retrospective, multicenter, descriptive study.

Objective: To describe the clinicopathological characteristics of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA).

Methods: In this multicenter case series, we retrospectively reviewed the medical records of RA patients who were newly diagnosed as having LPDs with or without biopsy confirmation between 2000 and 2017 in eight hospitals in Japan.

Results: We included 232 patients with LPDs.

Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load.

Phosphatidylinositol 3-kinase (PI3K) plays an important role in protein metabolism and cell growth. We here show that mice (M-PDK1KO mice) with skeletal muscle-specific deficiency of 3'-phosphoinositide-dependent kinase 1 (PDK1), a key component of PI3K signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of mechanical load-induced muscle hypertrophy. Whereas mechanical load-induced changes in gene expression were not affected, the phosphorylation of ribosomal protein S6 kinase (S6K) and S6 induced by mechanical load was attenuated in skeletal muscle of M-PDK1KO mice, suggesting that PDK1 regulates muscle hypertrophy not through changes in gene expression but through stimulation of kinase cascades such as the S6K-S6 axis, which plays a key role in protein synthesis.

Characteristics of rheumatoid arthritis with immunodeficiency-associated lymphoproliferative disorders to regress spontaneously by the withdrawal of methotrexate and their clinical course: A retrospective, multicenter, case-control study.

Objective: To investigate clinical characteristics and time course of lymphoproliferative disorders (LPDs) in rheumatoid arthritis (RA) patients after methotrexate (MTX) discontinuation, in those who achieved spontaneous regression (SR).

Methods: We retrospectively reviewed clinical data from RA patients with LPDs obtained from eight institutions between 2000 and 2017 and compared clinical and pathological findings between SR and non-SR groups.

Results: Among 232 RA patients with LPDs, 216 were treated with MTX at the onset of LPD and 144 (66.

Overall survival and post-spontaneous regression relapse-free survival of patients with lymphoproliferative disorders associated with rheumatoid arthritis: a multi-center retrospective cohort study.

Objectives: To clarify factors affecting 5-year survival rates and relapse rates after spontaneous regression (SR) of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA).

Methods: This retrospective longitudinal study comprised 232 patients with RA diagnosed with LPDs between January 2000 and March 2017 at eight hospitals in Japan. The Kaplan-Meier method was used to analyze survival and the Cox proportional hazard model was applied to identify predictive factors.

New Definitions of the Kilogram and the Mole: Paradigm Shift to the Definitions Based on Physical Constants.

The kilogram is the unit of mass and was defined in 1889 by the international prototype of the kilogram. The mole is the unit of amount of substance and was defined in 1960 by the number of atoms in 0.012 kg of C.

Treatment of rheumatoid arthritis after regression of lymphoproliferative disorders in patients treated with methotrexate: a retrospective, multi-center descriptive study.

Objectives: To identify the optimal treatment for rheumatoid arthritis (RA) after the regression of lymphoproliferative disorders (LPDs).

Methods: The subjects were 232 patients with RA who developed LPD between 2000 and 2017 at seven hospitals participating in the LPD-WG study. Kaplan-Meier and Cox proportional regression analyses were performed to determine the factors associated with the rate of LPD relapse and the retention of biological disease-modifying antirheumatic drugs (bDMARDs).

A case of systemic lupus erythematosus complicated by subclinical Cushing's syndrome: case report.

An 18-year-old female was diagnosed with subclinical Cushing's syndrome (CS) due to a left adrenal adenoma. When she was 20 years old, she developed lupus nephritis. She was treated with high-dose prednisolone (PSL) and soon developed the symptoms of CS.

Deep Learning-Based Swallowing Monitor for Realtime Detection of Swallow Duration.

Aspiration pneumonia is a life-threatening disease for the elderly. To prevent its risk, regular swallowing assessment is necessary; however, current screening tools for swallow assessment are not widely available and medical experts are insufficient. As a portable assessment tool, we have been developing a smartphone-based realtime monitoring device (GOKURI) which can evaluate swallowing ability based on swallow sounds.

Apelin/Apelin Receptor System: Molecular Characteristics, Physiological Roles, and Prospects as a Target for Disease Prevention and Pharmacotherapy.

Among the various orphan G protein-coupled receptors, apelin receptor (APJ), originally identified in the human genome as an orphan G-protein-coupled receptor, was deorphanised in 1998 with the discovery of its endogenous ligand, apelin. Apelin and APJ mRNA are widely expressed in peripheral tissues and the central nervous system in mammals. In this review, we discuss the characteristics, pharmacology, physiology, and pathology of the apelin/APJ system in mammals.

Development of a Machine Learning-Based Damage Identification Method Using Multi-Point Simultaneous Acceleration Measurement Results.

It is necessary to assess damage properly for the safe use of a structure and for the development of an appropriate maintenance strategy. Although many efforts have been made to measure the vibration of a structure to determine the degree of damage, the accuracy of evaluation is not high enough, so it is difficult to say that a damage evaluation based on vibrations in a structure has not been put to practical use. In this study, we propose a method to evaluate damage by measuring the acceleration of a structure at multiple points and interpreting the results with a Random Forest, which is a kind of supervised machine learning.

40 GHz continuous, precise, and low power-loss laser frequency sweep using an electro-optic modulator.

We propose and demonstrate a novel technique for precisely and widely sweeping the frequency of a continuous-wave laser. One of the modulation sidebands of a slave laser generated with an electro-optic modulator is phase-locked to a master laser; in this situation, the slave carrier component can be swept by sweeping the modulation frequency. It does not require beat signal detection at varying and/or high frequency, thus providing a robust and reliable laser frequency sweep.