Design of A Phase 1 Trial for Safety, Tolerability, Single‐ascending Dose, Multiple‐ascending Dose, Food Effect, and Pharmacokinetic Study of TML‐6, A Novel Oral Multi‐Target Drug, in Healthy Volunteers.

Background: Alzheimer’s disease (AD) is complex in pathogenesis and related to aging biology, especially in late‐onset AD. We identified a novel synthetic curcumin analog TML‐6 through the platform of 6 biomarkers of anti‐aging, anti‐inflammation, and anti‐Aβ as the potential AD drug candidate. TML‐6 exhibits multi‐target effects on AD pathogenesis, including the activation of NrF‐2, the regulation of autophagic machinery through mTOR, the inhibition of APP synthesis and reduction of Aβ, the upregulation of ApoE, and the inhibition of microglial activation.

Posteromedial olecranon impingement of the pitching elbow: Additional findings provided by CT.

Purpose: Posteromedial olecranon impingement (PMOI) is the most common diagnosis in baseball players with throwing-induced elbow injuries. CT imaging manifestations of PMOI have seldom been previously reported. Our purpose is to investigate the additional value of CT imaging in the evaluation of PMOI.

GaSb-based mid infrared photonic crystal surface emitting lasers.

We demonstrated for the first time above room temperature (RT) GaSb-based mid-infrared photonic crystal surface emitting lasers (PCSELs). The lasers, under optical pumping, emitted at λ(lasing)~2.3μm, had a temperature insensitive line width of 0.

Association between IPTA gene polymorphisms and hematological abnormalities in hepatitis C virus-infected patients receiving combination therapy.

Background/aims: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon α and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combina-tion treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the as-sociation between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy.

Circulating level of lipocalin 2 as a predictor of severity in patients with community-acquired pneumonia.

Background: The aim of this study was to investigate the differential plasma levels of lipocalin 2 (LCN2) and its complex with MMP-9 (where MMP is matrix metalloproteinase) before and after antibiotic treatment in hospitalized adult patients with community-acquired pneumonia (CAP).

Method: Plasma LCN2 and LCN2/MMP-9 complex levels were measured in 61 adult patients with CAP and 60 healthy controls using commercial enzyme-linked immunosorbent assay (ELISA).

Results: A decrease in the number of white blood cells (WBCs) and neutrophils and decreases in the levels of C-reactive protein (CRP), LCN2, and LCN2/MMP-9 complex were observed after antibiotic treatment.

Avoidance of Majorana resonances in periodic topological superconductor-nanowire structures.

Semiconducting nanowires in proximity to superconductors are promising experimental systems for Majorana fermions which may ultimately be used as building blocks for topological quantum computers. A serious challenge in the experimental realization of the Majorana fermion in these semiconductor-superconductor-nanowire structures is tuning the semiconductor chemical potential in close proximity to the metallic superconductor. We show that presently realizable structures in experiments with tunable chemical potential lead to Majorana resonances, which are interesting in their own right, but do not manifest non-Abelian statistics.

Anti-NMDA receptor encephalitis with the initial presentation of psychotic mania.

We report a 16-year-old girl with suspected psychotic mania, who subsequently developed amnesia, catatonia, oro-lingual dyskinesia, consciousness disturbance, seizure and respiratory failure. Repeated studies of the cerebrospinal fluid (CSF), viral culture and serology, brain MRI, single photon emission CT scan, and autoimmune profiles were all normal. She was finally diagnosed with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis based on the positive finding of NMDAR antibodies in CSF.

Early embolic events complicating intravenous thrombolysis for acute ischemic stroke.

Intravenous recombinant tissue plasminogen activator (IV rt-PA) is the only established thrombolytic therapy for acute ischemic stroke. However, secondary embolism after IV rt-PA for acute ischemic stroke is recognized as an uncommon complication, and the pathophysiology is unclear. We describe a 72-year-old man with acute infarction in the territory of left anterior cerebral artery who developed new infarction in the territory of right middle cerebral artery and acute peripheral arterial occlusion after IV rt-PA therapy.

Amyloid beta peptide-activated signal pathways in human platelets.

Amyloid beta peptide (amyloid-beta), which accumulates in the cerebral microvessels in an age-dependent manner, plays a key role in the pathogenesis of cerebral amyloid angiopathy. Platelets are an important cellular element in vasculopathy of various causes. Amyloid-beta may activate or potentiate platelet aggregation.

Multicomponent polymer coating to block photocatalytic activity of TiO2 nanoparticles.

Chemical grafting of anti-oxidant molecules with an additional hydrophobic polymer coating directly onto TiO(2) particle surfaces, using sonochemistry, is found to eliminate photocatalytic degradation enabling highly effective screening against UV radiation.

Inhibitory mechanisms of metallothionein on platelet aggregation in in vitro and platelet plug formation in in vivo experiments.

Metallothionein (MT) is a low-molecular-weight, cysteine-rich protein that contains heavy metals such as cadmium and zinc. The biological function of MT in platelets is not yet understood. Therefore, the aim of this study was to systematically examine the inhibitory mechanisms of metallothionein in platelet aggregation.

Effects of sphondin, isolated from Heracleum laciniatum, on IL-1beta-induced cyclooxygenase-2 expression in human pulmonary epithelial cells.

Recently, under large-scale screening experiments, we found that sphondin, a furanocoumarin derivative isolated from Heracleum laciniatum, possessed an inhibitory effect on IL-1beta-induced increase in the level of COX-2 protein and PGE(2) release in A549 cells. Accordingly, we examined in the present study the action mechanism of sphondin on the inhibition of IL-1beta-induced COX-2 protein expression and PGE(2) release in a human pulmonary epithelial cell line (A549). Pretreatment of cells with sphondin (10-50 microM) concentration-dependently attenuated IL-1beta-induced COX-2 protein expression and PGE(2) release.

Mechanisms involved in the antiplatelet activity of midazolam in human platelets.

Background: Midazolam is widely used as a sedative and anesthetic induction agent. The aim of this study was to systematically examine the inhibitory mechanisms of midazolam in platelet aggregation.

Methods: The inhibitory mechanisms of midazolam in platelet aggregation were explored by means of analysis of the platelet glycoprotein IIb-IIIa complex, phosphoinositide breakdown, intracellular Ca+2 mobilization, measurement of membrane fluidity, thromboxane B2 formation, and protein kinase C activity.