Osimertinib in a patient with non-small cell lung cancer and renal failure undergoing hemodialysis: a case report.

Osimertinib is a key drug for cancer patients with EGFR mutations. However, there is little information about its safety in cancer patients who require hemodialysis (HD) for chronic renal failure, despite notable increases in their numbers. Herein, we examined osimertinib safety in such a patient via pharmacokinetics analysis.

A single K-binding site in the crystal structure of the gastric proton pump.

The gastric proton pump (H,K-ATPase), a P-type ATPase responsible for gastric acidification, mediates electro-neutral exchange of H and K coupled with ATP hydrolysis, but with an as yet undetermined transport stoichiometry. Here we show crystal structures at a resolution of 2.5 Å of the pump in the E2-P transition state, in which the counter-transporting cation is occluded.

Real-time, non-destructive and in-field foliage yield and growth rate measurement in perennial ryegrass ( L.).

Background: In-field measurement of yield and growth rate in pasture species is imprecise and costly, limiting scientific and commercial application. Our study proposed a LiDAR-based mobile platform for non-invasive vegetative biomass and growth rate estimation in perennial ryegrass ( L.).

Genetic manipulation of autonomic nerve fiber innervation and activity and its effect on breast cancer progression.

The effects of autonomic innervation of tumors on tumor growth remain unclear. Here we developed a series of genetic techniques to manipulate autonomic innervation in a tumor- and fiber-type-specific manner in mice with human breast cancer xenografts and in rats with chemically induced breast tumors. Breast cancer growth and progression were accelerated following stimulation of sympathetic nerves in tumors, but were reduced following stimulation of parasympathetic nerves.

Refractory De Novo Multiple Cerebral Aneurysms After Radiotherapy and Multistaged "Open" Surgical Treatment for Low-Grade Glioma During Long-Term Follow-Up: A Case Report and Review of the Literature.

Background: Radiation-induced aneurysms have been previously reported; however, multiple and repeated de novo aneurysm formation chronologically and anatomically during long-term follow-up have not yet been observed. The pathogenesis of persistent radiation-induced vasculopathy is not fully understood.

Case Description: A 31-year-old woman presented with intraventricular hemorrhage due to rupture of a right internal carotid artery (ICA) aneurysm that developed 17 years after surgical resection of a low-grade glioma in the right frontal lobe and postoperative radiotherapy (focal, 50 Gy/25 fractions).

Three Structural Features of Functional Food Components and Herbal Medicine with Amyloid β42 Anti-Aggregation Properties.

Aggregation of amyloid β42 (Aβ42) is one of the hallmarks of Alzheimer's disease (AD). There are numerous naturally occurring products that suppress the aggregation of Aβ42, but the underlying mechanisms remain to be elucidated. Based on NMR and MS spectroscopic analysis, we propose three structural characteristics found in natural products required for the suppressive activity against Aβ42 aggregation (i.

An App knock-in mouse inducing the formation of a toxic conformer of Aβ as a model for evaluating only oligomer-induced cognitive decline in Alzheimer's disease.

Irie and colleagues identified a "toxic conformer", which possesses a turn structure at positions 22-23, among various conformations of Aβ and have been reporting its potent oligomeric capacity and neurotoxicity. This toxic conformer was detected in the brains of AD patients and AD model mice (Tg2576 line), and passive immunization targeting this conformer ameliorated the cognitive dysfunction in an AD model. In this study, we developed a novel AD mouse model (App) with Swedish mutation (NL), Iberian mutation (F), and mutation (P) overproducing E22P-Aβ, a mimic of the toxic conformer, utilizing the knock-in technique that well recapitulates the Aβ pathology of AD patients in mice and avoids the artificial phenotype observed in transgenic-type model mice.

Development of an LC-MS/MS-based method for quantitation of osimertinib in human plasma and cerebrospinal fluid.

The transitivity of osimertinib to cerebrospinal fluid (CSF) is of clinical concern. A quantitative LC-MS/MS method for the determination of osimertinib in human plasma and CSF was developed to evaluate its transitivity. The calibration range was 40-1000 nM in plasma and 0.

Pop2 phosphorylation at S39 contributes to the glucose repression of stress response genes, HSP12 and HSP26.

The S. cerevisiae Pop2 protein is an exonuclease in the Ccr4-Not complex that is a conserved regulator of gene expression. Pop2 regulates gene expression post-transcriptionally by shortening the poly(A) tail of mRNA.

Clinical and Radiological Characteristics of Intracranial Artery Dissection Using Recently Proposed Diagnostic Criteria.

Background: Data on the clinical and radiological characteristics of intracranial artery dissection (IAD) have remained limited. Our purpose was to reveal the clinical and radiological characteristics of IAD according to diagnostic criteria for IAD as recently reported by a group of international experts.

Methods: Patients were retrospectively enrolled using a prospective single-center stroke registry between 2011 and 2016.

Endocytosis of commensal antigens by intestinal epithelial cells regulates mucosal T cell homeostasis.

Commensal bacteria influence host physiology, without invading host tissues. We show that proteins from segmented filamentous bacteria (SFB) are transferred into intestinal epithelial cells (IECs) through adhesion-directed endocytosis that is distinct from the clathrin-dependent endocytosis of invasive pathogens. This process transfers microbial cell wall-associated proteins, including an antigen that stimulates mucosal T helper 17 (T17) cell differentiation, into the cytosol of IECs in a cell division control protein 42 homolog (CDC42)-dependent manner.

Awareness of Clenching and Underweight are Risk Factors for Onset of Crowding in Young Adults: A Prospective 3-Year Cohort Study.

Bruxism is a parafunctional activity that can seriously affect quality of life. Although bruxism induces many problems in the oral and maxillofacial area, whether it contributes to the onset of malocclusion remains unclear. The purpose of this prospective cohort study was to investigate the association between the onset of malocclusion and awareness of clenching during the daytime in young adults.

Morphologic determinant of tight junctions revealed by claudin-3 structures.

Tight junction is a cell adhesion apparatus functioning as barrier and/or channel in the paracellular spaces of epithelia. Claudin is the major component of tight junction and polymerizes to form tight junction strands with various morphologies that may correlate with their functions. Here we present the crystal structure of mammalian claudin-3 at 3.

Δ-Tetrahydrocannabinol elicited 22-kHz ultrasonic vocalization changes after air puff stimulus through CB receptor in adult rats.

Δ-Tetrahydrocannabinol (THC) is known to have various pharmacological effects mediated through activation of cannabinoid CB and CB receptors in rodents. In adult rats, 22- and 50-kHz ultrasonic vocalizations (USVs) serve as an effective communication system and as indicators of negative and positive states, respectively. The present study was performed to determine whether THC affects USVs in adult rats, and to determine the roles of cannabinoid receptors in these effects.

Frozen State of Sephadex Gels of Different Crosslink Density Analyzed by X-ray Computed Tomography and X-ray Diffraction.

Water in Sephadex (crosslinked dextran) gels is known to indicate different freezing behavior which is dependent on the density of the crosslinks, and water in a Sephadex G25 gel remains partially unfrozen during cooling and crystallizes during rewarming. The mechanism of anomalous ice crystallization during rewarming is still unclear. The objective of this study is to observe the ice grains that form in Sephadex beads and to comprehend their frozen state with a focus on the ice crystallization during rewarming.

Long-Term Treatment with Thrombomodulin Improves Functional Outcomes after Cerebral Ischemia Even if Administration is Delayed.

Our previous study indicated that recombinant human soluble thrombomodulin (rhsTM) could attenuate brain damage when administered as a bolus in the cerebral ischaemic early phase. Then, we considered that treatment with rhsTM may show therapeutic effects even when administered in the ischaemic delayed phase, because rhsTM has an action of inhibiting high-mobility group box 1 (HMGB1) as a late mediator of lethal systemic inflammation. This study was performed to investigate the effects of delayed treatment with rhsTM on ischaemic brain damage induced by high HMGB1 level in mice subjected to 4-hour middle cerebral artery occlusion (MCAO).

Characterization and pharmacokinetic evaluation of microcomposite particles of alpha lipoic acid/hydrogenated colza oil obtained in supercritical carbon dioxide.

The work reported here is an extension of our previous findings in which supercritical composite particles (SCP) of alpha lipoic acid (ALA) masked with hydrogenated colza oil (HCO) named as ALA/HCO/SCP were obtained by the modified particles from gas-saturated solutions (PGSS) process in supercritical carbon dioxide in order to obscure the unpleasant taste and odor of ALA. The masking effect on ALA/HCO/SCP was compared with the widely used mechano-chemically masked formulation of ALA and HCO named as MC-50F. In the present study, ALA/HCO/SCP particles were found to have a significant improvement in regard to bitterness, numbness, and smell compared to ALA bulk powders suggesting they were well coated.

The pathological challenge of establishing a precise diagnosis for pulmonary tumour thrombotic microangiopathy: identification of new diagnostic criteria.

Aims: Pulmonary tumour thrombotic microangiopathy (PTTM) is a fatal disease of patients with cancer that causes progressive pulmonary hypertension (PH). Its pathology is characterised by fibrocellular intimal proliferation and thrombosis caused by tumour emboli in microscopic pulmonary arteries. However, such PTTM-like lesions often appear incidentally.

EP receptor-associated protein regulates gluconeogenesis in the liver and is associated with hyperglycemia in diabetic mice.

Prostaglandin E receptor 4-associated protein (EPRAP) is a key molecule in suppressing inflammatory responses in macrophages. EPRAP is expressed not only in macrophages but also in hepatocytes; however, the role of EPRAP in hepatocytes has not yet been defined. To examine the physiological role of hepatic EPRAP in mice, we performed the glucose tolerance test and the hyperinsulinemic-euglycemic clamp in high-fat sucrose diet (HFSD)-fed wild-type (WT) and Eprap null mice.

Differential diagnosis of gallbladder polypoid lesions using contrast-enhanced ultrasound.

Purpose: The purpose of the study is to evaluate the utility of contrast-enhanced ultrasound (CEUS) for the differential diagnosis of gallbladder polypoid lesions (GPLs).

Methods: Thirty-six patients with GPLs (17 with gallbladder cancer, 19 with benign polyps) who underwent CEUS were enrolled in the study. The mean age of patients was 65.

Amyloid β toxic conformer has dynamic localization in the human inferior parietal cortex in absence of amyloid plaques.

Amyloid β (Aβ) plays a critical role in the pathogenesis of Alzheimer's disease. Nevertheless, its distribution and clearance before Aβ plaque formation needs to be elucidated. Using an optimized immunofluorescent staining method, we examined the distribution of Aβ in the post-mortem parietal cortex of 35 subjects, 30 to 65 years of age, APOE ε3/ε3, without AD lesions.

MIBG myocardial scintigraphy in progressive supranuclear palsy.

Background And Objectives: Meta-iodobenzylguanidine (MIBG) myocardial scintigraphy is an effective tool for distinguishing Parkinson's disease (PD) from other diseases accompanied by parkinsonism. Unlike other Parkinsonian diseases, in PD, MIBG accumulation in the heart tends to decrease. However, previous studies have reported that a decrease in MIBG accumulation also occurs in progressive supranuclear palsy (PSP).