Safety, pharmacokinetics, and pharmacodynamics of sofnobrutinib, a novel non-covalent BTK inhibitor, in healthy subjects: First-in-human phase I study.

Bruton's tyrosine kinase (BTK) is a potential therapeutic target for allergic and autoimmune diseases. This first-in-human phase I study evaluated safety, pharmacokinetic, and pharmacodynamic profiles of sofnobrutinib (formerly AS-0871), a highly selective, orally available, non-covalent BTK inhibitor, in healthy adult subjects. Single ascending doses (SAD; 5-900 mg) and multiple ascending doses (MAD; 50-300 mg twice daily [b.

Depressive symptoms, burnout, resilience, and psychosocial support in healthcare workers during the COVID-19 pandemic: A nationwide study in Japan.

Aim: The coronavirus disease 2019 pandemic has significantly impacted the mental health of healthcare workers. This study aimed to assess the mental health of healthcare workers and identify risk and protective factors.

Methods: We surveyed 48,031 healthcare workers at 63 Japanese Red Cross hospitals from December 15, 2022 to January 15, 2023.

A Single-Center Retrospective Study of Re-Transplantation After Allograft Failure in Kidney Transplant Recipients.

Background: This study aimed to examine the outcomes of kidney retransplantation in patients with allograft failure at Kyushu University.

Methods: We reviewed data from 1043 consecutive patients (including 1001 in a first kidney transplantation [KT] group and 42 in a second KT group) who had undergone KT alone at our institution between January 2008 and September 2022. We also studied immunologic risks and outcomes of patients who had undergone preoperative testing for KT at Kyushu University during the same period.

Optimization of lymphapheresis for manufacturing autologous CAR-T cells.

Collection of CD3+ lymphocytes via lymphapheresis is essential for manufacturing autologous chimeric antigen receptor (CAR) T cells. Optimization of timing and procedures for lymphapheresis for each patient is critical because patients often have progressive diseases and receive medications that could reduce T cell counts. We conducted a retrospective study of clinical data from 28 patients who underwent lymphapheresis for CD19-directed CAR-T therapy with tisagenlecleucel to identify factors that could affect CD3+ lymphocyte yields.

Altered cleavage plane orientation with increased genomic aneuploidy produced by receptor-mediated lysophosphatidic acid (LPA) signaling in mouse cerebral cortical neural progenitor cells.

The brain is composed of cells having distinct genomic DNA sequences that arise post-zygotically, known as somatic genomic mosaicism (SGM). One form of SGM is aneuploidy-the gain and/or loss of chromosomes-which is associated with mitotic spindle defects. The mitotic spindle orientation determines cleavage plane positioning and, therefore, neural progenitor cell (NPC) fate during cerebral cortical development.

Development of Highly Sensitive Biosensors of RAF Dimerization in Cells.

The BRAF inhibitors dabrafenib and vemurafenib induce remarkable clinical responses in patients with BRAF-mutated melanomas. However, adverse events, including the emergence of secondary tumors and drug resistance, have been reported. Studies have revealed that undesirable RAF dimerization induced by inhibitors promotes these adverse effects.

[Ultrasonography in Large-Vessel Arteritis].

Vasculitides are a group of diseases in which inflammation occurs in various vascular walls of the whole body, and ischemic symptoms are caused by stenoses and occlusions of blood vessels. Various parts of blood vessels of the whole body are affected, and the clinical manifestations are diverse. In the Chapel Hill Consensus Conference (CHCC) 2012, vasculitides are classified into seven categories.

Living-donor kidney transplant in T-cell and B-cell flow cytometry crossmatch-positive patients.

Objectives: Complement-dependent cytotoxic crossmatch is an important indicator for kidney transplant. However, there is controversy about treatment for flow cytometry crossmatch-positive cases.

Materials And Methods: This was a retrospective study of 127 living-donor kidney transplant recipients from May 2007 to July 2011.

No difference in adherence to paroxetine between depressed patients with early remission and those with late remission based on monitoring of plasma paroxetine concentrations.

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat both anxiety disorders and depressive disorders. However, nonadherence to SSRIs is a major issue in recurrence. In the present study, we investigated paroxetine adherence in depressed patients by monitoring the plasma paroxetine concentrations between patients with rapid and those with a late response to paroxetine treatment.

Pitavastatin improves plasma pentraxin 3 and arterial stiffness in atherosclerotic patients with hypercholesterolemia.

Objective: To investigate the effect of pitavastatin on asymptomatic atherosclerosis in patients with hypercholesterolemia.

Methods: Thirty-five outpatients with hypercholesterolemia (61.5+/-12.

Rapid response to paroxetine is associated with plasma paroxetine levels at 4 but not 8 weeks of treatment, and is independent of serotonin transporter promoter polymorphism in Japanese depressed patients.

In the present study, we investigated the relationship between the serotonin transporter gene linked polymorphic regions (5-HTTLPR) or plasma paroxetine levels and clinical response to paroxetine in depressed patients. Sixty patients who met the DSM-IV criteria for major depressive disorder were enrolled in the study. Twenty-two were male and 38 were female, with ages ranging from 25 to 71 (mean +/- SD = 42 +/- 16) years.

Enhanced expression of NADPH oxidase Nox4 in human gliomas and its roles in cell proliferation and survival.

Reactive oxygen species (ROS) have been attracting attention as mediators of various cell-signaling pathways. Nox-family NADPH oxidases have proven to be a major source of ROS production in various cell types and have crucial roles in various physiological and pathological processes. In this study, we show that Nox4, a member of Nox family, is prominently expressed in various neuroepithelial tumors by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemical studies.

Lipopolysaccharide induced expression of pentraxin 3 in human neutrophils and monocyte-derived macrophages.

Pentraxin 3 (PTX3) is a prototype protein of long pentraxin. PTX3 is produced by various cells, such as monocytes/macrophages (Mphis) in response to lipopolysaccharide (LPS) and proinflammatory signals. We performed immunoblotting, immunohistochemical staining, reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA) of PTX3 in human monocyte-derived Mphis and neutrophils.

Increased expression of long pentraxin PTX3 in inflammatory bowel diseases.

The aims of this study were to investigate the expression of pentraxin-3 in inflamed gastrointestinal tissue in patients with inflammatory bowel diseases and to elucidate the usefulness of plasma pentraxin-3 level as an inflammation marker in patients with inflammatory bowel diseases. Pentraxin-3 immunoreactivity was found in infiltrating neutrophils and vessels in the inflamed gut. Plasma pentraxin-3 concentration in patients with active inflammatory bowel diseases was significantly higher than that of normal subjects and patients with inactive inflammatory bowel diseases.

Effects of acute paroxetine treatment on the consumption of cigarette smoking and caffeine in depressed patients.

In the present study, we examined the effects of acute treatment with paroxetine on the consumption of cigarette smoking and caffeine in 65 patients who met the DSM-IV criteria for major depressive disorder (M/F: 28/37, age: 48 +/- 15 years). Plasma levels of cotinine or caffeine were analysed using high-performance liquid chromatography (HPLC). The amount of cigarette smoking and plasma levels of cotinine, but not caffeine, decreased 4 weeks after paroxetine treatment.

Enhanced expression of DNA topoisomerase II genes in human medulloblastoma and its possible association with etoposide sensitivity.

Medulloblastoma (MB) is the most common malignant neuroepithelial tumor of childhood. The DNA topoisomerase II (Topo II) inhibitor etoposide has been widely used for the treatment of MBs; however, it remains unknown whether MB cells are more sensitive to etoposide than other malignant neuroepithelial tumor cells. In this study, we tested the chemosensitivities of malignant neuroepithelial tumors (26 glioblastomas, 9 anaplastic astrocytomas, and 5 MBs) to etoposide and vincristine using the succinate dehydrogenase inhibition test and found that MB cells are more sensitive to etoposide and more resistant to vincristine than other tumor cells.

Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris.

Objective: Plasma pentraxin 3 (PTX3) levels are increased in patients with acute myocardial infarction, yet its involvement in unstable angina pectoris (UAP) remains unclear. To critically evaluate the role of PTX3 in UAP, a sensitive and precise measurement of PTX3 concentration is needed.

Methods And Results: We established a high sensitive plasma ELISA assay system for the detection of PTX3 using monoclonal antibodies.

Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on preimplantation mouse embryos.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental contaminant that can exert developmental toxicity. To investigate the stage-specific effects of TCDD on preimplantation embryos, we exposed mouse embryos to TCDD at different stages (1-, 2-, and 8-cell) and collected them at different stages of development (the 1- or 2-, 8-cell, and blastocyst stage, respectively). Semiquantitative RT-PCR revealed increased constitutive gene expression of the arylhydrocarbon receptor (AhR) and AhR nuclear translocator (Arnt) at the 1-cell stage, decreased expression at the 2- to 8-cell stage, and increased expression again at the blastocyst stage, and addition of TCDD to media did not affect their mRNA levels.