Primary Allylic Amine Synthesis via Pd-Catalyzed Direct Amination of Allylic Alcohols with Ammonium Acetate.

Pd/DPEphos-catalyzed direct amination of allylic alcohols with readily available ammonium acetate as a nitrogen source provides access to convenient and scalable syntheses of primary allylic amines with high monoallylation selectivity. Mechanistic studies revealed that ammonium acetate functions as a Brønsted acid to activate the hydroxyl groups and inhibit overreaction.

Successful left ventricular lead placement by way of an azygos vein for a patient performing cardiac resynchronization therapy implantation with an occluded left subclavian vein: A case report.

Central venous obstruction following pacemaker implantation is not uncommon and can prove challenging in the case of a system upgrade to a cardiac resynchronization therapy pacemaker (CRT-P). We describe the case of a patient who underwent a successful upgrading procedure of a pacemaker to a CRT-P in the presence of an occluded left subclavian vein and superior vena cava, using collateral veins that drained into right atrium.

O- and N-Selective Electrophilic Activation of Allylic Alcohols and Amines in Pd-Catalyzed Direct Alkylation.

Catalytic control of chemoselectivity is crucial in the synthesis of highly functionalized compounds. Although there are reports of efficient chemoselective reactions of alcohols and amines as nucleophiles, there are no reports of the chemoselective activation of alcohols and amines as electrophiles. In this study, highly O- and N-selective electrophilic activation of allylic alcohols and amines was achieved in Pd-catalyzed direct allylic alkylation.

The costimulatory activity of Tim-3 requires Akt and MAPK signaling and its recruitment to the immune synapse.

Expression of the transmembrane protein Tim-3 is increased on dysregulated T cells undergoing chronic activation, including during chronic infection and in solid tumors. Thus, Tim-3 is generally thought of as an inhibitory protein. We and others previously reported that under some circumstances, Tim-3 exerts paradoxical costimulatory activity in T cells (and other cells), including enhancement of the phosphorylation of ribosomal S6 protein.

Skeletal muscle mass is associated with glycemic variability in patients with ST-segment elevation myocardial infarction.

Skeletal muscle function has been studied to determine its effect on glucose metabolism; however, its effect on glycemic variability (GV), which is a significant glycemic marker in patients with coronary artery disease, is unknown. The aim of the present study was to elucidate the association between skeletal muscle mass and GV. Two hundred and eight consecutive ST-segment elevation myocardial infarction (STEMI) patients who underwent continuous glucose monitoring to evaluate mean amplitude of glycemic excursion (MAGE) as GV and a dual-energy X-ray absorptiometry (DEXA) to evaluate skeletal muscle mass were enrolled.

Clinical impact of admission urinary 8-hydroxydeoxyguanosine level for predicting cardiovascular mortality in patients with acute coronary syndrome.

The aim of the present study was to determine whether urinary 8-hydroxydeoxyguanosine (8-OHdG), which is a marker of oxidative stress, can predict future cardiovascular death in patients with acute coronary syndrome (ACS). A total of 551 consecutive patients with ACS who underwent admission urinary 8-OHdG measurements were enrolled in this study. The patients were divided into 2 groups according to the optimal cutoff value of admission urinary 8-OHdG determined by a receiver-operating characteristics curve for the prediction of cardiovascular death: a high admission urinary 8-OHdG group, 169 patients with admission urinary 8-OHdG ≥ 17.

PIK3IP1/TrIP restricts activation of T cells through inhibition of PI3K/Akt.

Phosphatidylinositol-3 kinases (PI3Ks) modulate cellular growth, proliferation, and survival; dysregulation of the PI3K pathway can lead to autoimmune disease and cancer. PIK3IP1 (or transmembrane inhibitor of PI3K [TrIP]) is a putative transmembrane regulator of PI3K. TrIP contains an extracellular kringle domain and an intracellular domain with homology to the inter-SH2 domain of the PI3K regulatory subunit p85, but the mechanism of TrIP function is poorly understood.

Glycemic variability determined with a continuous glucose monitoring system can predict prognosis after acute coronary syndrome.

Background: Impaired glucose metabolism is an established risk factor for coronary artery disease. Previous studies revealed that glycemic variability (GV) is also important for glucose metabolism in patients with acute coronary syndrome (ACS). We explored the association between GV and prognosis in patients with ACS.

Non-Covalent Loading of Anti-Cancer Doxorubicin by Modularizable Peptide Self-Assemblies for a Nanoscale Drug Carrier.

We prepared nanoscale, modularizable, self-assembled peptide nanoarchitectures with diameters less of than 20 nm by combining β-sheet-forming peptides tethering a cell-penetrating peptide or a nuclear localization signal sequence. We also found that doxorubicin (Dox), an anti-cancer drug, was non-covalently accommodated by the assemblies at a ratio of one Dox molecule per ten peptides. The Dox-loaded peptide assemblies facilitated cellular uptake and subsequent nuclear localization in HeLa cells, and induced cell death even at low Dox concentrations.

Roles of aromatic side chains and template effects of the hydrophobic cavity of a self-assembled peptide nanoarchitecture for anisotropic growth of gold nanocrystals.

Gold nanocrystals are promising as catalysts and for use in sensing/imaging systems, photonic/plasmonic devices, electronics, drug delivery systems, and for photothermal therapy due to their unique physical, chemical, and biocompatible properties. The use of various organic templates allows control of the size, shape, structure, surface modification and topology of gold nanocrystals; in particular, currently the synthesis of gold nanorods requires a cytotoxic surfactant to control morphology. To control the shape of gold nanocrystals, we previously demonstrated the de novo design and synthesis of a β-sheet-forming nonapeptide (RU006: Ac-AIAKAXKIA-NH2, X=L-2-naphthylalanine, Nal) and the fabrication of gold nanocrystals by mixing RU006 and HAuCl4 in water.

Glycemic Variability on Continuous Glucose Monitoring System Correlates With Non-Culprit Vessel Coronary Plaque Vulnerability in Patients With First-Episode Acute Coronary Syndrome - Optical Coherence Tomography Study.

Background: Glycemic variability (GV) is associated with coronary plaque rupture at the culprit lesion in acute myocardial infarction (AMI). The present study determined the relationship between GV and coronary plaque vulnerability in the non-culprit vessel.

Methods And Results: The present prospective study involved 46 patients with first-episode acute coronary syndrome (ACS) who underwent optical coherence tomography in the non-culprit vessel.

Association between blood glucose variability and coronary plaque instability in patients with acute coronary syndromes.

Background: Blood glucose variability is receiving considerable attention as a new risk factor for coronary artery disease. This study aimed to investigate the association between blood glucose variability and coronary plaque tissue characteristics.

Methods: In 57 patients with acute coronary syndrome, integrated backscatter intravascular ultrasound (IB-IVUS) and gray-scale IVUS were performed before balloon dilatation or stent implantation in the culprit vessels.

Glycemic Variability on Continuous Glucose Monitoring System Predicts Rapid Progression of Non-Culprit Lesions in Patients With Acute Coronary Syndrome.

Background: Although rapid progression (RP) of coronary artery disease (CAD) has been shown to be a powerful predictor of cardiovascular events, predictors of RP are not fully understood in patients with acute coronary syndrome (ACS).

Methods and results: We prospectively investigated the clinical impact of glycemic variability (GV), as determined on continuous glucose monitoring system (CGMS), on RP of non-culprit lesions in 88 patients with ACS. RP was defined as ≥10% diameter reduction in a pre-existing stenosis ≥50%; ≥30% diameter reduction in a stenosis <50%; development of a new stenosis ≥30% in a previously normal segment; or progression of any stenosis to total occlusion.

Glycemic Variability Determined by Continuous Glucose Monitoring System Predicts Left Ventricular Remodeling in Patients With a First ST-Segment Elevation Myocardial Infarction.

Background: Impaired glucose metabolism plays an important role in patients with acute myocardial infarction, but the clinical significance of glycemic variability (GV) early after the onset of ST-segment elevation myocardial infarction (STEMI) remains to be fully elucidated.

Methods And Results: We prospectively investigated the clinical impact of GV, as determined by a continuous glucose monitoring system (CGMS), on left ventricular remodeling (LVR) assessed by cardiac magnetic resonance imaging (CMR) in 69 patients (63±13 years, 59 men) with a first reperfused STEMI within 12 h of onset. All patients were equipped with a CGMS when in a stable phase after admission and underwent repeat CMR at baseline and 7 months follow-up.

Chronic treatment with valproic acid or sodium butyrate attenuates novel object recognition deficits and hippocampal dendritic spine loss in a mouse model of autism.

We recently showed that prenatal exposure to valproic acid (VPA) in mice causes autism-like behavioral abnormalities, including social interaction deficits, anxiety-like behavior and spatial learning disability, in male offspring. In the present study, we examined the effect of prenatal VPA on cognitive function and whether the effect is improved by chronic treatment with VPA and sodium butyrate, histone deacetylase inhibitors. In addition, we examined whether the cognitive dysfunction is associated with hippocampal dendritic morphological changes.

Utility of noninvasive endothelial function test for prediction of deep vein thrombosis after total hip or knee arthroplasty.

Background: Venous thromboembolism (VTE) is a common and sometimes lethal postoperative complication of arthroplasty. Endothelial dysfunction is important in the pathogenesis of thrombus formation. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) can noninvasively evaluate endothelial function.

Effect of prenatal valproic acid exposure on cortical morphology in female mice.

We have recently shown that prenatal valproic acid (VPA) exposure causes autism spectrum disorders-like behavioral abnormalities and Nissl-positive cell loss in both prefrontal and somatosensory cortices in male mice. We have also found that VPA-induced social interaction deficits are observed in male but not female offspring. This study demonstrated that the exposure to VPA at embryonic day 12.

Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid.

Maternal use of valproic acid (VPA) during pregnancy has been implicated in the aetiology of autism spectrum disorders in children, and rodents prenatally exposed to VPA showed behavioural alterations similar to those observed in humans with autism. However, the exact mechanism for VPA-induced behavioural alterations is not known. To study this point, we examined the effects of prenatal exposure to VPA and valpromide, a VPA analog lacking histone deacetylase inhibition activity, on behaviours, cortical pathology and histone acetylation levels in mice.