A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids.

The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes.

Relationship between Initial Telomere Length, Initial Telomerase Activity, Age, and Replicative Capacity of Nucleus Pulposus Chondrocytes in Human Intervertebral Discs: What Is a Predictor of Replicative Potential?

There is evidence that telomere length (TL), telomerase activity (TA), and age are related to the replicative potential of human nucleus pulposus chondrocytes (NPCs). However, it has not yet been established if any of these factors can serve as predictors of the replicative potential of NPCs. To establish predictors of the replicative potential of NPCs, we evaluated potential relationships between replicative capacity of NPCs, initial TL (telomere length at the first passage), initial TA (telomerase activity at the first passage), and age.

Extracorporeal cardiopulmonary resuscitation in bedside echocardiography-diagnosed massive pulmonary embolism.

Acute pulmonary embolism (PE) is one of the major causes of inhospital cardiac arrest as well as out-of-hospital cardiac arrest. Bedside diagnosis of acute PE in the emergency department (ED) can be challenging, especially in a cardiac arrest setting. Even if the early diagnosis of an acute massive PE had been made, hemodynamic instability may be worsened unless obstructive shock gets resolved.

Preoperative anxiety about spinal surgery under general anesthesia.

Purpose: No study has investigated preoperative anxiety about spinal surgery under general anesthesia. The purposes of this study were (1) to determine how many patients have preoperative anxiety about spinal surgery and general anesthesia, (2) to evaluate the level of anxiety, (3) to identify patient factors potentially associated with the level of anxiety, and (4) to describe the characteristics of the anxiety that patients experience during the perioperative period.

Methods: This study was performed in 175 consecutive patients undergoing laminectomy for lumbar stenosis or discectomy for herniated nucleus pulposus under general anesthesia.

Synthesis of (±)-spongiolactone enabling discovery of a more potent derivative.

An eleven-step synthesis of (±)-spongiolactone from 1,3-cyclohexanedione is reported that relies on a diastereoselective, nucleophile-catalyzed aldol lactonization (NCAL) process with an advanced ketoacid intermediate that installed the anticipated β-lactone pharmacophore of the natural product. In addition, a stereoselective cyclohexenyl zinc addition to a substituted cyclohexanone simultaneously installed two fully substituted vicinal stereocenters. The reported synthesis enabled preliminary structure-activity studies that revealed a regio- and stereoisomeric derivative of spongiolactone with greater antiproliferative activity towards a leukemia (K562) cell line.

Solid-solution nanocrystallite formation by high-energy milling.

Solid-solution nanocrystalline powders were prepared by the high-energy milling of Ti alloys with graphite. The B1 structure (NaCl-like structure) phases, (Ti, Cr)C and (Ti, Al)C, were formed during the milling process of Ti-Cr + graphite and Ti-Al + graphite, and the synthetic procedures were investigated in terms of the phase evolution from XRD data. The (Ti, Al)C phase was obtained after milling for 20 hr at BPR = 40:1 (under a more severe condition), while the (Ti, Cr)C phase formed after milling for 20 hr at BPR = 20:1 (a relatively soft condition).

Complications and revision rate compared by type of total elbow arthroplasty.

Background: This study evaluates the long-term results, including complication and revision rates, of different types of total elbow arthroplasty (TEA) with an average follow up of 13 years.

Methods: Since 1984, a total of 84 primary TEAs have been performed in 77 patients at our institution. The patient's average age was 54.

A new method for the identification and quantification of magnetite-maghemite mixture using conventional X-ray diffraction technique.

The electrical explosion of Fe wire in air produced nanoparticles containing the binary mixture of magnetite (Fe(3)O(4)) and maghemite (γ-Fe(2)O(3)). The phase identification of magnetite and maghemite by the conventional X-ray diffraction method is not a simple matter because both have the same cubic structure and their lattice parameters are almost identical. Here, we propose a convenient method to assess the presence of magnetite-maghemite mixture and to further quantify its phase composition using the conventional peak deconvolution technique.

One Year Follow-up Result of Doppler-guided Hemorrhoidal Artery Ligation and Recto-Anal Repair in 97 Consecutive Patients.

Purpose: Doppler-guided hemorrhoidal artery ligation and recto-anal repair (DG-HAL & RAR) is known for low recurrence, high patient satisfaction, and less postoperative pain. The purpose of this study is to analyze the 1-year follow-up results in patients who underwent a DG-HAL & RAR and to establish the benefits of the procedure.

Methods: Among the hemorrhoid patients who were admitted to our hospital from March 2008 to May 2010 and who underwent a DG-HAL & RAR, 97 patients who were followed up for a year were investigated.

Rapid consolidation of nanostuctured TiCu compounds.

TiCu nanopowder was produced using an electrical wire explosion method and subsequently consolidated into dense nanostuctured TiCu by a high frequency induction heated sintering method. The consolidation was accomplished by the combination of an induced current and a high mechanical pressure within two minutes. This process results in very quick densification to near the theoretical density and prohibits grain growth in nano-structured materials.

Differences in prognostic factors between early and advanced gastric cancer.

Background/aims: The aim of this study was to assess any differences in the prognostic factors affecting long term survival in early gastric cancer (EGC) and advanced gastric cancer (AGC).

Methodology: The prognostic factors affecting long term survival between EGC and AGC were evaluated.

Results: Based on the result of multivariate analysis, the variables related with poor prognosis in patient with EGC were ages of more than 60 (p=0.

How can a single rescuer adequately deliver tidal volume with a manual resuscitator? An improved device for delivering regular tidal volume.

Objectives: A bag-valve mask (BVM) device is used as one of the first-line pieces of equipment in emergency situations. However, cardiopulmonary support providers do not recognise the exact tidal volume during procedures, and squeezing methods of BVM may not deliver the same tidal volume each time. To supply a regular and sustained tidal volume, adequate finger points were marked on the surface of a BVM.

Total synthesis of (-)-belactosin C and derivatives via double diastereoselective tandem mukaiyama aldol lactonizations.

[reaction: see text] The enantioselective synthesis of (-)-belactosin C and derivatives was accomplished in a concise manner employing the tandem, Mukaiyama aldol-lactonizaton (TMAL) process. One approach involved a distal double diastereoselective TMAL reaction with a dipeptide glyoxamide, whereas a second approach involved amide coupling of a dipeptide with a beta-lactone carboxylic acid, obtained via the TMAL process employing a chiral silyl ketene acetal. Notable improvements in diastereoselectivity were achieved in a proximal double diastereoselective TMAL process.