Substrates, regulation, cellular functions, and disease associations of P4-ATPases.

P4-ATPases, a subfamily of the P-type ATPase superfamily, play a crucial role in translocating membrane lipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet. This process generates and regulates transbilayer lipid asymmetry. These enzymes are conserved across all eukaryotes, and the human genome encodes 14 distinct P4-ATPases.

Influence of Worsening Renal Function and Baseline Chronic Kidney Disease on Clinical Outcomes in Patients With Chronic Coronary Syndromes: Insights From the REAL-CAD Study.

Background: The effect of worsening renal function and baseline chronic kidney disease (CKD) on outcomes in patients with chronic coronary syndrome in the setting of optimal medical therapy remains unknown.

Methods And Results: The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease) study is a prospective, multicenter, randomized trial of high-dose (pitavastatin 4 mg/day) or low-dose (pitavastatin 1 mg/day) statin therapy in 12 118 patients with chronic coronary syndrome. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or unstable angina requiring hospitalization (major adverse cardiac and cerebral events [MACCE]).

Impact of CT-angiography derived plaque characteristics on cardiac events in patients with a negative invasive fractional flow reserve.

Background: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for chronic coronary syndromes (CCS) improves outcomes compared with angiography-guided PCI, however cardiac events still occur during long-term follow-up of FFR-negative patients. In the PREVENT study preventive PCI reduced cardiac-events in lesions which were FFR-negative (FFR > 0.80) and had intracoronary imaging defined vulnerable plaque.

Intracranial atherosclerotic disease mechanism indicates poor outcomes of thrombectomy in acute cerebral infarction with large vessel occlusion: A matched cohort study.

Background: Thrombectomy is a standard treatment for acute large vessel occlusion (LVO); however, its effectiveness in treating LVO related to intracranial atherosclerosis disease (ICAD) remains uncertain. This study aimed to compare thrombectomy outcomes in ICAD-related and embolic LVO, focusing on patients with similar symptom severities upon hospital admission.

Methods: This retrospective study was conducted at Jikei University Hospital and Jikei University Kashiwa Hospital between October 2017 and March 2023.

Novel phosphatidylinositol flippases contribute to phosphoinositide homeostasis in the plasma membrane.

Phosphatidylinositol is a precursor of various phosphoinositides, which play crucial roles in intracellular signaling and membrane dynamics and have impact on diverse aspects of cell physiology. Phosphoinositide synthesis and turnover occur in the cytoplasmic leaflet of the organellar and plasma membranes. P4-ATPases (lipid flippases) are responsible for translocating membrane lipids from the exoplasmic (luminal) to the cytoplasmic leaflet, thereby regulating membrane asymmetry.

Missense Variations of ATP8B2 Impair Its Phosphatidylcholine Flippase Activity.

P4-ATPases comprise a family of lipid flippases that translocate lipids from the exoplasmic (or luminal) to the cytoplasmic leaflet of biological membranes. Of the 14 known human P4-ATPases, ATP8B2 is a phosphatidylcholine flippase at the plasma membrane, but its physiological function is not well understood. Although ATP8B2 could interact with both CDC50A and CDC50B, it required only the CDC50A interaction for its exit from the endoplasmic reticulum and subsequent transport to the plasma membrane.

Effectiveness of Intravenous Cyclophosphamide in a Patient With Anti-amphiphysin Autoimmunity Presenting With Bulbar Palsy and Cerebellar Ataxia: A Case Report.

Anti-amphiphysin antibody is a rare paraneoplastic autoantibody. A case of a 74-year-old man with anti-amphiphysin antibody and multiple symptoms, including bulbar palsy along with cerebellar ataxia, who responded to treatment with intravenous cyclophosphamide is reported. The patient presented with progressive unsteady gait and difficulty in swallowing food and water for three months.

Bathing-Related Ischemic Stroke: Association between Stroke Subtype and Cerebral Small Vessel Disease.

Aims: Bathing-related ischemic stroke (BIS) is sometimes fatal. However, its mechanisms and risk factors remain unclear. We aimed to identify the incidence of stroke subtypes in BIS, and clarify the impact of cerebral small vessel disease (CSVD) on BIS.

Effects and safety of high-frequency rTMS in subacute ischemic stroke patients.

Objective: Although high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has shown benefits in chronic stroke, its application in subacute ischemic stroke remains underexplored. This study aims to investigate the effects and safety of lesion-side HF-rTMS in subacute ischemic stroke.

Methods: Prospective lesion-side HF-rTMS was conducted on consecutive ischemic stroke patients within 3 days of onset from February 2019 to June 2022.

A facile method for monitoring sphingomyelin synthase activity in HeLa cells using liquid chromatography/mass spectrometry.

Sphingomyelin synthase (SMS) is a sphingolipid-metabolizing enzyme involved in the synthesis of sphingomyelin (SM) from ceramide (Cer). Recent studies have indicated that SMS is a key therapeutic target for metabolic diseases such as fatty liver, type 2 diabetes, atherosclerosis, and colorectal cancer. However, very few SMS inhibitors have been identified because of the limited sensitivity and selectivity of the current fluorescence-based screening assay.

Construction of Ideal One-Dimensional Spin Chains by Topochemical Dehydration/Rehydration Route.

One-dimensional (1D) Heisenberg antiferromagnets are of great interest due to their intriguing quantum phenomena. However, the experimental realization of such systems with large spin remains challenging because even weak interchain interactions induce long-range ordering. In this study, we present an ideal 1D = 5/2 spin chain antiferromagnet achieved through a multistep topochemical route involving dehydration and rehydration.

Small ischemic lesions accompanying intracerebral hemorrhage: The underlying influence of old lacunes and polyunsaturated fatty acids.

Background And Aims: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs.

Glucosylceramide flippases contribute to cellular glucosylceramide homeostasis.

Lipid transport is an essential cellular process with importance to human health, disease development, and therapeutic strategies. Type IV P-type ATPases (P4-ATPases) have been identified as membrane lipid flippases by utilizing nitrobenzoxadiazole (NBD)-labeled lipids as substrates. Among the 14 human type IV P-type ATPases, ATP10D was shown to flip NBD-glucosylceramide (GlcCer) across the plasma membrane.

Thin aortic arch plaque is associated with the development of atrial fibrillation for embolic stroke of undetermined source in patients with an insertable cardiac monitor.

Background And Objective: This study's objective is to investigate whether mild aortic arch plaque is associated with the development of atrial fibrillation (AF) in stroke patients with embolic stroke of undetermined source (ESUS) during the first year following the implantation of an insertable cardiac monitor (ICM).

Methods: The participants in this cross-sectional observational study were consecutive patients with ESUS, even after transesophageal echocardiography. We assessed the relationship between the thickness of the participants' aortic arch plaque and AF detected after ICM implantation.

Thermal multiferroics in all-inorganic quasi-two-dimensional halide perovskites.

Multiferroic materials, particularly those possessing simultaneous electric and magnetic orders, offer a platform for design technologies and to study modern physics. Despite the substantial progress and evolution of multiferroics, one priority in the field remains to be the discovery of unexplored materials, especially those offering different mechanisms for controlling electric and magnetic orders. Here we demonstrate the simultaneous thermal control of electric and magnetic polarizations in quasi-two-dimensional halides (K,Rb)MnCl, arising from a polar-antipolar transition, as evidenced using both X-ray and neutron powder diffraction data.

Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease.

Gaucher disease (GD) is a recessively inherited lysosomal storage disorder characterized by a deficiency of lysosomal glucocerebrosidase (GBA1). This deficiency results in the accumulation of its substrate, glucosylceramide (GlcCer), within lysosomes. Here, we investigated lysosomal abnormalities in fibroblasts derived from patients with GD.

Deep and infratentorial cerebral microbleeds are related to wake-up stroke by large-artery atherosclerosis and cardioembolism.

Background And Aims: Circadian variability of blood pressure (BP) and hypercoagulation in the morning have been proposed as underlying mechanisms of wake-up stroke (WUS). The aim was to determine the impact of cerebral microbleeds (CMBs), showing BP fluctuation and background hypercoagulability, on WUS.

Methods: Consecutive patients with acute ischemic stroke onset-to-door time within one week were screened.

Follow-Up Diffusion-Weighted Image Reveals Delayed Appearance of Ischemic Lesions in Suspected Transient Ischemic Attack.

Introduction: In patients suspected of transient ischemic attack (TIA), it is not uncommon to find no lesion on the diffusion-weighted image (DWI) on admission but a delayed appearance on the follow-up DWI.

Methods: Enrolled patients met the following criteria: (1) MRI performed within 24 hours of onset and seven days after admission; (2) National Institutes of Health Stroke Scale (NIHSS) score ≦4 on admission; (3) pre-stroke modified Rankin scale (mRS) score of 0-1. Patients were divided as follows: no lesion on the first DWI and a new lesion on the second DWI (delayed-specified ischemic stroke; DSIS); and no lesion on either the first or second DWI (well-screened TIA; WSTIA).

[A case of cryptogenic new-onset refractory status epilepticus (NORSE) in which cerebrospinal fluid IL-6 was elevated with increased seizure frequency early in the disease: a case report].

A 25-year-old male presented with clonic seizures three days following a fever. The patient developed status epilepticus and required mechanical ventilation and intravenous anesthesia. The patient's epileptic seizures persisted despite administering intravenous anesthesia and multiple anti-epileptic drugs.

Large Perpendicular Magnetic Anisotropy Induced by an Intersite Charge Transfer in Strained EuVOH Films.

Perovskite oxides O continue to be a major focus in materials science. Of particular interest is the interplay between and cations as exemplified by intersite charge transfer (ICT), which causes novel phenomena including negative thermal expansion and metal-insulator transition. However, the ICT properties were achieved and optimized by cationic substitution or ordering.

Urinary Immunoglobulin G Is a Novel Biomarker for Atherosclerotic Burden in Mild Acute Ischemic Stroke Patients.

Aims: Urinary immunoglobulin G (IgG) may be a stronger marker of atherosclerosis than microalbuminuria are because urinary IgG reflects proteinuria level and size-selectivity loss. Microalbuminuria-not urinary IgG-is associated with mild acute ischemic stroke (MAIS).

Methods: Using the Jikei University School of Medicine Stroke Registry, we selected and screened patients with symptomatic acute ischemic stroke (onset-to-door time ≤ 24 h).

The REMIT scale: A novel prediction scale for embolism in hyperacute stroke with large vessel occlusion.

Background And Purpose: Large vessel occlusion (LVO) in hyperacute ischemic stroke occurs mainly by one of two mechanisms, embolism or atherosclerosis. However, the mechanism is difficult to identify prior to treatment. We aimed to investigate the factors associated with embolic LVO in hyperacute ischemic stroke, and to develop a preoperative predictive scale for the event.

Diagnostic Yield of Bone Window Computed Tomography and Cerebral Angiography Testing Congenital Bilateral Hypoplasia of the Internal Carotid Artery.

We herein report a case of congenital bilateral hypoplasia of the internal carotid artery (ICA) that was diagnosed by bone window computed tomography (CT) and cerebral angiography. A 23-year-old woman presented with left dominant quadriplegia. Brain magnetic resonance imaging showed not only massive infarcts in the anterior circulation but also poor depiction of the bilateral ICAs.