Concordance Between Pharmaceuticals and Medical Devices Agency Review and Ministry of Health, Labour and Welfare Decision Among New Drug Applications in Japan.

New drug applications (NDAs) in Japan are reviewed by the Pharmaceuticals and Medical Devices Agency (PMDA). Those that pass the review are subsequently subject to deliberation by the Ministry of Health, Labour and Welfare Pharmaceutical Affairs and Food Sanitation Councils (MHLW-PAFSC), and the MHLW legislatively grants approval based on its positive opinions. However, little is known regarding the relationship between the PMDA review and the MHLW decision.

Removal of α1-Microglobulin Using Post-Dilution Online Hemodiafiltration with Polymethylmethacrylate Membrane: An Open-Label, Single-Arm Study.

Introduction: The removal of low- and medium-molecular-weight proteins has been improved with online hemodiafiltration (OL-HDF) and hemodialysis using high-flux membranes; however, the outcomes of patients with end-stage kidney disease (ESKD) undergoing dialysis treatment are still worse than in the general population. α1-Microglobulin (α1-m), with a molecular weight of 33,000 Da, may contribute to dialysis-related disorders and mortality. However, the removal is insufficient even with current OL-HDF using the polysulfone (PS) membrane, which is common in Japan.

Effect of Locally Delivered Minocycline on the Profile of Subgingival Bacterial Genera in Patients with Periodontitis: A Prospective Pilot Study.

This prospective pilot study aimed to evaluate the effect of minocycline-HCl ointment (MO), locally delivered as an adjunct to scaling and root planing (SRP), on subgingival microflora. A total of 59 periodontitis patients received SRP as an initial periodontal therapy. In the selected periodontal pockets with probing depths (PD) of 6−9 mm, the sites that exhibited a positive reaction following a bacterial test using an immunochromatographic device were subsequently treated with MO (SRP + MO group, n = 25).

The relationship between dental metal allergy, periodontitis, and palmoplantar pustulosis: An observational study.

Purpose: This study aimed to investigate the relationship between dental metal allergy, periodontitis, and palmoplantar pustulosis among patients from a dental metal allergy clinic over a period of 8 years.

Methods: This study included 436 patients who visited our dental metal allergy clinic between April 1, 2009 and March 31, 2016. Diagnoses of skin diseases, periodontal records, dental metal series patch test results, and electron probe microanalysis (EPMA) data were obtained from medical records.

Impact of Local Drug Delivery of Minocycline on the Subgingival Microbiota during Supportive Periodontal Therapy: A Randomized Controlled Pilot Study.

The aim of this study was to examine the effect of adjunct local minocycline administration on the microbiological parameters of subgingival plaque samples in the residual periodontal pockets. Ten chronic periodontitis patients under a supportive periodontal therapy regimen were recruited. After subgingival debridement, either 2% minocycline gel, Periocline™, (Test Group) or a placebo (Control Group) was administered to the selected sites once a week for three weeks.

Sporadic Triple A (Allgrove) Syndrome with Novel Tandem Mutations.

In triple A (Allgrove) syndrome, motor neuron disease is a co-morbid condition. We herein report a 38-year-old Japanese man with triple A (Allgrove) syndrome and novel tandem mutations: a novel c.881delT deletion mutation and c.

Dashcam-captured moment of right hemispheric stroke.

A bus driver presented with neurological abnormalities following a driving mishap. He was diagnosed cardioembolic stroke. The bus was equipped with a dashboard camera that recorded the moment when the patient suffered the stroke.

Evaluating recanalization of relevant lenticulostriate arteries in acute ischemic stroke using high-resolution MRA at 7T.

Background: Occluded major intracranial arteries can spontaneously recanalize in patients with acute ischemic stroke mainly due to embolic mechanisms. However, it remains unknown whether recanalization can occur in perforating arteries, such as lenticulostriate arteries. Therefore, in the present study, we assessed changes suggesting recanalization of the lenticulostriate arteries in patients with acute ischemic stroke of the lenticulostriate artery territory using high-resolution magnetic resonance angiography (HR-MRA) at 7T.

Computational Fluid Dynamics Analysis of Lateral Striate Arteries in Acute Ischemic Stroke Using 7T High-resolution Magnetic Resonance Angiography.

Background: Infarcts in the lateral striate artery (LSA) territory can be caused by several pathological changes, including lipohyalinosis and microatheroma. However, fluid dynamic effects on these changes remain unknown. Thus, we investigated whether the fluid dynamic metrics of the LSAs were altered in patients with acute ischemic stroke using computational fluid dynamics (CFD) analysis.

Corrigendum to "Indirect regulation of PCSK9 gene in inflammatory response by infection" [Heliyon 5 (1) (January 2019) e01111].

[This corrects the article DOI: 10.1016/j.heliyon.

Indirect regulation of PCSK9 gene in inflammatory response by infection.

Pro-protein convertase subtilisin/kexin type 9 (PCSK9), a secreted serine protease, regulates serum low-density lipoprotein (LDL) cholesterol levels by targeting the degradation of LDL receptor (LDLR) in the liver. Although previous reports describe elevated levels of PCSK9 in patients with periodontitis, the mechanisms that trigger this increase in serum PCSK9 levels and induce the related inflammatory response remain unclear. In an -deficient mouse of infection, nucleic acid antigen recognition via Toll-like receptors was found to promote PCSK9 production, suggesting an indirect role for tumor necrosis factor-α as an inducer of PCSK9 in contrast to that reported in previous studies.

Detecting lenticulostriate artery lesions in patients with acute ischemic stroke using high-resolution MRA at 7 T.

Background: Recent advances in high-resolution (HR) magnetic resonance angiography (MRA) using ultrahigh-field systems enable direct visualization of the lenticulostriate arteries (LSAs), which had been hardly achieved by conventional MRA. Hence, by using HR-MRA at 7 T, we attempted to assess occlusive changes in the LSAs in patients with LSA territorial infarcts.

Methods: We prospectively examined 34 consecutive patients with acute ischemic stroke in the LSA territory using a 7 T scanner.

T1-Weighted Magnetic Resonance Carotid Plaque Imaging: a Comparison between Conventional and Fast Spin-Echo Techniques.

Background: Magnetic resonance imaging is widely used to evaluate the intraplaque components of the cervical carotid artery. The non-gated T1-weighted spin-echo (SE) technique has been reported to have an excellent ability for discriminating stable and unstable plaques. However, the diagnostic performance of various SE-based techniques remains unclear.

Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota.

Periodontitis has been implicated as a risk factor for metabolic disorders such as type 2 diabetes, atherosclerotic vascular diseases, and non-alcoholic fatty liver disease. Although bacteremias from dental plaque and/or elevated circulating inflammatory cytokines emanating from the inflamed gingiva are suspected mechanisms linking periodontitis and these diseases, direct evidence is lacking. We hypothesize that disturbances of the gut microbiota by swallowed bacteria induce a metabolic endotoxemia leading metabolic disorders.

Effect of Porphyromonas gingivalis infection on post-transcriptional regulation of the low-density lipoprotein receptor in mice.

Background: Periodontal disease is suggested to increase the risk of atherothrombotic disease by inducing dyslipidemia. Recently, we demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9), which is known to play a critical role in the regulation of circulating low-density lipoprotein (LDL) cholesterol levels, is elevated in periodontitis patients. However, the underlying mechanisms of elevation of PCSK9 in periodontitis patients are largely unknown.

Increased serum PCSK9 concentrations are associated with periodontal infection but do not correlate with LDL cholesterol concentration.

Background: Periodontal disease increases the risk of atherothrombotic disease, and high concentrations of low density lipoprotein (LDL) cholesterol are considered to be involved; however, the underlying mechanisms are largely unknown. Recent studies demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in circulating LDL cholesterol concentrations. The aim of the present study is to analyze serum PCSK9 concentrations and their relation to lipoprotein concentrations in periodontitis patients.

Chronic oral infection with Porphyromonas gingivalis accelerates atheroma formation by shifting the lipid profile.

Background: Recent studies have suggested that periodontal disease increases the risk of atherothrombotic disease. Atherosclerosis has been characterized as a chronic inflammatory response to cholesterol deposition in the arteries. Although several studies have suggested that certain periodontopathic bacteria accelerate atherogenesis in apolipoprotein E-deficient mice, the mechanistic link between cholesterol accumulation and periodontal infection-induced inflammation is largely unknown.

Low-pH-induced transformation of bilayer membrane into bicontinuous cubic phase in dioleoylphosphatidylserine/monoolein membranes.

Cubic biomembranes, nonbilayer membranes with connections in three-dimensional space that have a cubic symmetry, have been observed in various cells. Interconversion between the bilayer liquid-crystalline (L(alpha)) phase and cubic phases attracted much attention in terms of both biological and physicochemical aspects. Herein we report the pH effect on the phase and structure of dioleoylphosphatidylserine (DOPS)/monoolein (MO) membranes under a physiological ion concentration condition, which was revealed by small-angle X-ray scattering (SAXS) measurement.

High-level tryptophan accumulation in seeds of transgenic rice and its limited effects on agronomic traits and seed metabolite profile.

Metabolic manipulation of plants to improve their nutritional quality is an important goal of plant biotechnology. Expression in rice (Oryza sativa L.) of a transgene (OASA1D) encoding a feedback-insensitive alpha subunit of rice anthranilate synthase results in the accumulation of tryptophan (Trp) in calli and leaves.

Characterization of tryptophan-overproducing potato transgenic for a mutant rice anthranilate synthase alpha-subunit gene (OASA1D).

Potato plants (Solanum tuberosum cv. May Queen) transgenic for OASA1D, which encodes a point mutant of an alpha-subunit of rice (Oryza sativa) anthranilate synthase (AS, EC 4.1.

Quantification of indole-3-acetic acid and amino acid conjugates in rice by liquid chromatography-electrospray ionization-tandem mass spectrometry.

A method for quantifying indole-3-acetic acid (IAA) and its conjugates with the six amino acids, Ala, -Asp, -Ile, -Glu, -Phe and -Val, in rice (Oryza sativa) by using high-performance liquid chromatography coupled with electrospray ionization and tandem mass spectrometry (HPLC-ESI-MS/MS) is described. Samples from the rice plant or callus were treated with 80% acetone in water containing 2.5 mM diethyl dithiocarbamate.