Leiomyogenic and Cardiomyogenic Differentiation Potential of Human Adipose-derived Stem Cells

Coronary artery disease is the leading cause of death in industrialized countries. Strategies to treat atherosclerotic coronary artery disease include coronary artery bypass grafting, which is often complicated by vein graft occlusion or stenosis. Severely occluded vein grafts can completely obstruct blood flow to the myocardium, resulting in a myocardial infarction, and eventually lead to heart failure. Heterotopic heart transplantation remains the treatment of choice for end-stage heart failure, however its widespread applicability is limited by the chronic shortage of donor organs. The therapeutic potential of stem cells in cardiac repair following myocardial infarction has generated a great deal of interest. Many types of stem/progenitor cells including embryonic stem cells and bone marrow-derived mesenchymal stem cells (MSCs) have been used to regenerate the infracted heart with promising results. Adipose tissue is an abundant source of multipotent stem cells that can be easily obtained from liposuction waste tissue. The yield of stem cells per gram of fat is higher when compared with marrow-derived MSCs, making adipose tissue an attractive source of autologous stem cells for cardiovascular cell therapies. The goal of this research effort was to examine the differentiation potential of adipose-derived stem cells (ASCs) along the leiomyogenic and cardiomyogenic lineages. ASCs were extracted from human subcutaneous adipose tissue from female donors during elective abdominoplasty, cultured in the presence of biomolecules responsible for vascular and cardiac development, and subjected to uniaxial cyclic strain in magnitudes comparable to the in vivo conditions. Protein and gene expression of smooth muscle- and cardiomyocyte-specific markers were assessed via immunoctytochemistry, Western blot analysis, and RT-PCR. Our results indicated that uniaxial cyclic strain inhibited cell proliferation, resulted in alignment of ASCs perpendicular to the direction of strain, and down-regulated protein expression of early smooth muscle cell markers A-SMA and h1-calponin. Transforming growth factor B1 significantly up-regulated the expression of A-SMA and h1-calponin in ASCs. Cardiac-specific proteins sarcomeric A-actinin, troponin-I, troponin-T were undetected in ASCs exposed to demethylation agent 5-azacytidine. Expression of cardiac transcription factors Nkx2.5 and GATA4 were also absent. These results suggest that human ASCs may not be capable of cardiomyogenic differentiation via exposure to 5-azacytidine

Clinical Characteristics and Risk Factors for Mortality in Patients with Meningitis Caused by Staphylococcus aureus and Vancomycin Minimal Inhibitory Concentrations Against These Isolates

Background/PurposeBacterial meningitis caused by Staphylococcus aureus is uncommon but has a high mortality rate. The aims of this study were to better understand the clinical manifestations of S. aureus meningitis, to identify the risk factors for mortality in the affected patients, and to determine the levels of vancomycin minimal inhibitory concentrations (MICs) against these pathogens.MethodsA retrospective study of patients with S. aureus meningitis hospitalized between December 2000 and December 2008 was made, and vancomycin MICs against S. aureus isolates was determined using Etest.ResultsAmong 37 patients with S. aureus meningitis, fever was most commonly observed. Twenty-six patients (70.3%) had received prior neurosurgery, and 24 (64.9%) patients were suffering from methicillin-resistant S. aureus (MRSA) infections. The vancomycin MIC of 2 μg/mL was found in 23 (74.2%) of 31 S. aureus isolates available for testing. Excluding three patients who did not receive antibiotics for their S. aureus meningitis the mortality rate was 35.3% in the 34 remaining patients, with concurrent infective endocarditis an independent risk factor for mortality (odds ratio = 21.00; 95% confidence interval, 1.834-240.515; p = 0.01).ConclusionPatients with S. aureus meningitis and concurrent infective endocarditis were at a higher risk of mortality. A vancomycin MIC of 2 μg/mL against a substantial number of S. aureus isolates that grew from the cerebrospinal fluid suggests the importance of obtaining trough vancomycin concentrations of 15-20 μg/mL for the treatment of MRSA meningitis

Intramodality and Intermodality Registration of the Liver

Radiological imaging of the liver is an important medical problem. The ever increasing amount of data acquired when imaging the liver makes integration of information desirable and crucial in building up a comprehensive diagnostic picture of the patient. The foundation of all such image integration is image registration.Image registration is the process of aligning images so that corresponding features can easily be related, including: (1) landmark-driven methods, (2) surface-based methods, and (3) voxel similarity-based methods. A challenge with registering the liver is that the liver moves within the abdomen with respiration. Therefore any effective alignment of the liver must first separate the liver from the remainder of the image. With this as a constraint, the goal of this research effort was to determine the feasibility and efficacy of surface-based and voxel similarity-based schemes in registering abdominal CT and MR images with and without contrast.A multi-scale surface fitting technique was implemented based on the Head and Hat algorithm. Equivalent surfaces from the in vivo images were extracted manually. The hand segmentation approach was validated by ensuring the volume of the liver of each image from the same patient was consistently within +/- 7% of one another. The registration transformation was determined by iteratively transforming the hat with respect to the head surface, until the closest fit of the hat onto the head was found. In addition, registration of in vivo CT and MR images was performed using a multi-resolution mutual information scheme distributed with the ITK Insight software package (National Library of Medicine, Bethesda, MD). As an independent measure of registration accuracy, the mean displacement of automatically selected point landmarks was evaluated. For the multi-resolution mutual information approach, mean misregistrations were in the range of 7.7-8.4mm for CT-CT intramodality registration, 8.2mm for MR-MR intramodality registration, and 14.0-18.9mm for CT-MR intermodality registration. For the Head and Hat surface registration scheme, mean misregistrations were in the range of 9.6-11.1mm for CT-CT intramodality registration, 9.2-12.4mm for MR-MR intramodality registration, and 15.2-19.0mm for MR-CT intermodality registration

Fluoroquinolone therapy for bloodstream infections caused by extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae

AbstractBackground/PurposeFor extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae infections, carbapenems are recommended as first line therapy, and clinical data on the therapeutic efficacy of fluoroquinolones (FQs) is limited. This study compares the efficacy of FQs and carbapenems for bloodstream infections caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae.MethodsBetween 2008 and 2010, adults with ESBL-producing E. coli or K. pneumoniae bacteremia at two medical centers were reviewed. Adults receiving definitive FQ or carbapenem therapy were compared in a propensity score-matched analysis, and 30-day mortality was the primary endpoint.ResultsA total of 299 patients were eligible. Patients receiving a FQ (n = 24), either ciprofloxacin or levofloxacin, had a lower 30-day mortality rate than those with carbapenem therapy (8.3%, 2/24 vs. 23.3%, 64/275; p = 0.12). Multivariate regression analysis revealed that a critical illness [Pitt bacteremia score ≥ 4 points; odds ratio (OR), 7.09; p < 0.001], rapidly fatal underlying disease (OR, 5.73; p < 0.001), and hospital-associated infection (OR, 2.57; p = 0.01) were independently associated with 30-day mortality. By contrast, FQ definitive therapy was a protective factor compared with carbapenems (OR, 0.18; p = 0.04). There were 72 matched cases with carbapenem therapy in a propensity score-matched analysis, and a difference in the 30-day mortality rate of two groups was noted (8.3% vs. 29.2%; p = 0.05).ConslusionFor ESBL-producing E. coli or K. pneumoniae bacteremia, ciprofloxacin or levofloxacin, if active in vitro, can be considered as a carbapenem-sparing alternative

Where are the Atoms in Quasicrystals? Experimental and Theoretical Studies of Ternary and Quaternary Approximants

Problems concerning complete structural characterization of quasicrystals involve locating the atomic positions as well as determining the distribution of elements at each site. Quasicrystalline approximants provide models for potential building units of quasicrystals, but a clear determination of the elementaldecorations in such approximants also remains incomplete. We report experimental and theoretical studies of new, quaternary Bergman phases in the Li-Mg-Zn-Al system and a new, quasicrystalline approximant Li10Mg6Zn31Al3 (A16M34-type). A theoretical model using averaged Mulliken populations provides a means to track the segregation of elements (and vacancies) onto different sites as a function of valence electron concentration. As the Li content decreases, vacancies begin to occur at a specific site in the Bergman structure. The new approximant demonstrates how truncated tetrahedra can play an important role in forming clusters with possible fivefold symmetry in quasicrystalline structures

Attenuation of Guided Wave Propagation by the Insulation Pipe

Pipeline systems are widely used in gas, refinery, chemical and petro-chemical industries, which usually carry high pressure, high temperature or even highly corrosive fluids. Cracks and corrosion are often found at the outer or inner surface of pipeline and can lead to a serious thinning of wall thickness. Leaks or sudden failures of pipes can cause injuries, fatalities and environmental damage. Ultrasonic nondestructive techniques are available for the detection of wall loss associated with defects in the pipe. Unfortunately, a high proportion in pipelines of these industrial are insulated, so that even external corrosion cannot readily be detected by the conventional ultrasonic testing (single position measurement) without the removal of the insulation, which in most case is time-consuming and cost expensive. Especially in typically industrial plants, there are hundreds of kilometers of pipelines can be in operation. Making inspection of full pipelines is virtually impossible in industrial plants. There is therefore a quick reliable method for the detection of corrosion under insulation (CUI). This technique, called guided wave, employs a pulseecho system applied at a single location of a pipe where only a small section of insulation need to be removed, using waves propagation along the pipe wall. The changes in the response signal indicate the presence of an impedance change in the pipe. The shape and axial location of defects and features in the pipe are also determined by reflected signals and their arrival times. Propagation distance of many tens of meters can readily be obtained in steel pipes [1-6]. Since these guided waves are cylindrical Lamb waves along the pipe, no lateral spreading can occur and the propagation is essentially one-dimensional. In a uniform pipe, their amplitude with propagation distance is therefore only reduced by the material attenuation of the steel [7]

Dynamic Mechanical Response of Biomedical 316L Stainless Steel as Function of Strain Rate and Temperature

A split Hopkinson pressure bar is used to investigate the dynamic mechanical properties of biomedical 316L stainless steel under strain rates ranging from 1 × 103 s−1 to 5 × 103 s−1 and temperatures between 25°C and 800°C. The results indicate that the flow stress, work-hardening rate, strain rate sensitivity, and thermal activation energy are all significantly dependent on the strain, strain rate, and temperature. For a constant temperature, the flow stress, work-hardening rate, and strain rate sensitivity increase with increasing strain rate, while the thermal activation energy decreases. Catastrophic failure occurs only for the specimens deformed at a strain rate of 5 × 103 s−1 and temperatures of 25°C or 200°C. Scanning electron microscopy observations show that the specimens fracture in a ductile shear mode. Optical microscopy analyses reveal that the number of slip bands within the grains increases with an increasing strain rate. Moreover, a dynamic recrystallisation of the deformed microstructure is observed in the specimens tested at the highest temperature of 800°C

Community-onset bacteremia in kidney transplant recipients: The recipients fare well in terms of mortality and kidney injury

BackgroundBloodstream infection is not uncommon in kidney transplant recipients (KTRs) and is associated with mortality, graft loss, and increased medical expenses. Whether these septic patients are more vulnerable to serious complications, resistant strains, or worse clinical outcomes than other patient groups in the community-onset settings remains undetermined.MethodsA retrospective study was conducted at a medical center in southern Taiwan. Community-onset bacteremia in the KTRs and a control population at the emergency department were identified. Demographic data, clinical characteristics, bacteremic pathogens, antimicrobial resistance, and clinical outcomes were recorded.ResultsForty-one bacteremic episodes in the KTRs and 82 episodes in control patients were studied. The KTR group had younger age, fewer malignancies, more urosepsis (61% vs. 22%, p = 0.004), and fewer biliary tract infections (0% vs. 13.4%, p = 0.018). Escherichia coli was the most commonly isolated pathogen in both the groups (51.2% and 41.5%, respectively). No Klebsiella pneumoniae bacteremia was noted in the KTRs, compared with 14 (17.1%) episodes in the control group (p = 0.010). Antimicrobial resistance profiles of bacteremic pathogens were similar (all p > 0.6). The KTRs with community-onset bacteremia did not have a worse outcome (in-hospital mortality rate: 2.4% vs. 10%, p = 0.172) nor more incomplete resolution of kidney injury after acute kidney injury events (21.1% vs. 25%, p > 0.99) than the control group.ConclusionKTRs with community-onset bacteremia did not fare worse in terms of clinical outcome and kidney injury