Synthesis of Telechelic Oligomers via Atom Transfer Radical Polymerization, 1

Summary: Atom Transfer Radical Polymerization (ATRP) of styrene was carried out at 110 °C using various substituted 2‐bromoisobutyrates as initiators and the homogeneous catalyst CuBr/1,1,4,7,10,10‐hexamethyltriethylenetetramine (HMTETA). Telechelic oligomers were obtained by coupling the bromo terminated polymers using Cu(0)/PMDETA catalyst at 90 °C. The products were characterized by ¹H NMR and MALDI‐TOF and some unsaturated polymer chains were observed. They could originate from either disproportionation reaction or dehydrohalogenation of halogen terminated oligomers during MALDI analysis. Using this method, polymers with hydroxy, acid, or ester end groups were synthesized in a range of molecular weights from 1 000 to 13 000 g · mol^?1. Coupling efficiency was between 79 and 100%, depending on the structure of the initiator.

Coupling reaction of substituted polystyrenes using Cu(0)/PMDETA system at 90 °C.     

Classification of multi-class motor imagery with a novel hierarchical SVM algorithm for brain–computer interfaces

Pattern classification algorithm is the crucial step in developing brain–computer interface (BCI) applications. In this paper, a hierarchical support vector machine (HSVM) algorithm is proposed to address an EEG-based four-class motor imagery classification task. Wavelet packet transform is employed to decompose raw EEG signals. Thereafter, EEG signals with effective frequency sub-bands are grouped and reconstructed. EEG feature vectors are extracted from the reconstructed EEG signals with one versus the rest common spatial patterns (OVR-CSP) and one versus one common spatial patterns (OVO-CSP). Then, a two-layer HSVM algorithm is designed for the classification of these EEG feature vectors, where “OVO” classifiers are used in the first layer and “OVR” in the second layer. A public dataset (BCI Competition IV-II-a)is employed to validate the proposed method. Fivefold cross-validation results demonstrate that the average accuracy of classification in the first layer and the second layer is 67.5 ± 17.7% and 60.3 ± 14.7%, respectively. The average accuracy of the classification is 64.4 ± 16.7% overall. These results show that the proposed method is effective for four-class motor imagery classification.     

Trends in postacute myocardial infarction management and mortality in patients with diabetes. A population-based study from 1995 to 2001

OBJECTIVE:

To compare trends in coronary revascularization use and case fatality rate (CFR) following acute myocardial infarction in patients with and without diabetes.

METHODS:

A retrospective study of 77,552 patients, 20 years of age or older (25% with diabetes), who were hospitalized for a first acute myocardial infarction in the province of Quebec between April 1995 and December 2001 was conducted. Administrative databases were used to identify patients and assess outcomes.

RESULTS:

Compared with patients without diabetes, patients with diabetes underwent more coronary artery bypass graft (CABG) surgeries (11.1% versus 8.3%; P<0.0001) but fewer percutaneous coronary interventions (17.1% versus 20.2%; P<0.0001). The use of percutaneous coronary intervention increased substantially over time in both populations, driven mainly by an increase during the index admission (20.6% versus 16.6% per year; P=0.1144 in patients with and without diabetes, respectively). The use of CABG during the index admission increased markedly among patients with diabetes compared with those without (10.3% versus 5.3% per year; P=0.0072); however, at one-year following discharge, CABG use remained stable in patients with diabetes and fell in those without (−0.7% versus −5.3% per year; P=0.2046). Concomitantly, patients with diabetes presented a similar decline in CFR compared with patients without diabetes. The decline was more pronounced during the index admission (−5.0% versus −4.1% per year; P=0.282) than at one-year following discharge (−2.5% versus −2.5% per year; P=0.629) in patients with and without diabetes, respectively. However, fatal outcome remained higher in patients with diabetes than without, with an adjusted RR of 1.21 (95% CI 1.18 to 1.24) at one-year follow-up.

CONCLUSION:

Overall, coronary revascularization use and CFR improved over time in patients with diabetes. Nevertheless, the mortality rate in patients with diabetes remains higher than in patients without diabetes, indicating that additional progress is required to improve the poorer prognosis in this population.     

The contribution of combined crystalloid and colloid osmosis to fluid and sodium management in peritoneal dialysis

The achievement of euvolemia is essential to the successful management of peritoneal dialysis patients. However, the concern that hypertonic glucose exchanges may have a role in long-term changes to the peritoneal membrane has lead to an alternative strategy to enhance ultrafiltration (UF) over the long dwell by combining crystalloid and colloid osmosis. This review summarizes the experience of mixing glucose or amino acids with polyglucose (icodextrin), with particular focus given to data from studies using glucose/icodextrin in combinations of 1.36%/7.5% and 2.61%/6.8%. Both combinations demonstrate a significant increment of UF volume and sodium removal compared with the component osmotic agents used individually over long dwells, with the 2.61%/6.8% mixture having an effect over dwells extending to 15 h. Hypothetically, the mechanism of the enhanced UF is the attenuation by the colloid osmotic force of the backflow of water through small pores from dialysate to the peritoneal capillary circulation once the crystalloid osmotic force has dissipated. This experience provides promising data that deserves further examination in longer term clinical studies.     

The use of bioluminescence resonance energy transfer for the study of therapeutic targets: application to tyrosine kinase receptors

During recent years, the bioluminescence resonance energy transfer (BRET) methodology has emerged as a powerful technique for the study of protein-protein interactions. This review focuses on recent work demonstrating the power of BRET for the study of tyrosine kinase receptors, using insulin and IGF-1 receptors as models. The authors show that BRET can be used to monitor ligand-induced conformational changes within homodimeric insulin and IGF-1 receptors, as well as heterodimeric insulin/IGF-1 hybrid receptors. BRET can also be used to study, in real time and in living cells, the interaction of tyrosine kinase receptors with cellular partners negatively or positively involved in the regulation of intracellular signalling (protein tyrosine phosphatases, molecular adaptors). In addition, BRET can be used to develop high-throughput screening assays for the search of molecules with therapeutic interest and could, therefore, constitute a valuable tool for laboratories involved in drug discovery.     

Rapid Curbing of a Vancomycin-Resistant Enterococcus faecium Outbreak in a Nephrology Department

Background and objectives: Vancomycin-resistant enterococci (VRE) are recovered with increasing frequency among patients with chronic renal failure, making VRE a major concern in nephrology departments, especially for patients who are treated by hemodialysis. We report herein the successful aggressive management of a VRE outbreak in a nephrology department.Design, setting, participants, & measurements: An Enterococcus faecium vanB strain was isolated from a peritoneal dialysis solution from an inpatient. Immediately, infection control measures were enforced and active screening was performed for all contact patients. Carriers were isolated, and patients were divided into three cohorts: Positive, contact, and noncontact patients. We then performed a case-control study to understand risk factors for VRE carriage comparing VRE carriers with contact patients who were negative for VRE.Results: A total of 14 VRE-positive and 125 VRE-negative contact patients were identified. VRE-positive patients were more likely to receive hemodialysis and have longer hospital stays in nephrology. VRE-positive patients more often had a central venous catheter for a longer period of time and received more antibiotics than VRE-negative patients. Treatment with large-spectrum β-lactams and number of days in the nephrology ward were significantly associated with a higher risk for VRE carriage by using multivariate analysis.Conclusions: These findings suggest that case mix, longer hospital stays, and antibiotic use are major risk factors for VRE acquisition. In addition, it demonstrates that strict enforcement of isolation precautions and cohorting associated with active screening are successful to curb the transmission of VRE in renal units despite continuous colonization pressure.More than 70% of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used to treat these infections (1). Among multidrug-resistant organisms (MDROs), glycopeptide-resistant or vancomycin-resistant enterococci (VRE) became a concern throughout the world during the 1990s. Most enterococcal infections are caused by Enterococcus faecalis. The remaining infections are mostly caused by E. faecium, a species that is more likely than E. faecalis to be resistant, even to antibiotics of last resort as glycopeptides. Resistance to the latter compounds is most frequently of vanA phenotype (i.e., acquired and high-level resistance to vancomycin and teicoplanin). The VanB phenotype, characterized by variable levels of resistance to vancomycin with usually in vitro susceptibility to teicoplanin, is less common (1).Early studies dealing with VRE outbreaks in the United States revealed that most patients were in intensive care units (2–4); however, VRE is now recovered with increasing frequency among patients with chronic renal failure (2,5), making VRE a major concern in nephrology departments, especially for patients who are treated by hemodialysis. VRE was seldom isolated in French hospitals until recently (6–9). For example, fewer than five VRE carriers are identified each year in our institution, a large French University Hospital, and most of them are sporadic cases. We report herein the successful aggressive management of a VRE outbreak in the nephrology department of our hospital and the results of a case-control study to understand risk factors for VRE carriage in this specific epidemiologic setting.     

A homogenous assay to monitor the activity of the insulin receptor using Bioluminescence Resonance Energy Transfer

Insulin exerts its biological effects through a plasma membrane receptor that possesses a tyrosine kinase activity. Binding of insulin to its receptor induces a conformational change that stimulates the autophosphorylation of the receptor on tyrosine residues. This autophosphorylation stimulates the tyrosine kinase activity of the receptor toward intracellular substrates involved in the transmission of the signal. The discovery of pharmacological agents that specifically activate the tyrosine kinase activity of the insulin receptor will be of great importance for the treatment of insulin-resistant or insulin-deficient patients. We have developed a procedure based on Bioluminescence Resonance Energy Transfer (BRET) to monitor the activation state of the insulin receptor. Human insulin receptor cDNA, was fused to either Renilla luciferase or yellow fluorescent protein coding sequences. Fusion insulin receptors were partially purified by wheat-germ lectin chromatography from HEK-293 cells co-transfected with these constructs. The conformational change induced by insulin on its receptor could be detected as an energy transfer (BRET signal) between Renilla luciferase and yellow fluorescent protein. BRET signal paralleled insulin-induced autophosphorylation of the fusion receptor. Dose-dependent effects of insulin, insulin-like growth factor 1 and epidermal growth factor on BRET signal were in agreement with known pharmacological properties of these ligands. Moreover, an antibody, which activated the autophosphorylation of the receptor, had similar effects on BRET signal. This methodology allows for rapid analysis of the effects of agonists on insulin receptor activity and could, therefore, be used in high-throughput screening for the discovery of molecules with insulin-like properties.     

Kinetic Studies and Temperature-Induced Morphological Changes of Peptide Decorated Nano-Objects via Polymerization-Induced Self-Assembly

In the present work, combining polymerization-induced self-assembly (PISA) with self-assembling peptides (SAPs) peptide−polymer hybrid nanostructures are prepared, harnessing the advantages of PISA and the self-assembling driving force of SAPs. A tripeptide methacrylamide denoted as MAm-GFF, where MAm, G, and F stand for methacrylamide, glycine, and phenylalanine, is copolymerized with glycerol monomethacrylate (GMA) by reversible addition−fragmentation chain transfer polymerization (RAFT) in dimethylformamide to produce a P(GMA₆₂-stat-(MAm-GFF)₇) macromolecular chain transfer agent (macro-CTA). This peptide-containing macro-CTA is then successfully chain-extended with poly(2-hydroxypropyl methacrylate) (PHPMA) by aqueous dispersion PISA, forming P(GMA₆₂-stat-(MAm-GFF)₇)-b-PHPMA₂₇ self-assembled objects. The impacts of temperature and monomer conversion on the morphologies formed during the PISA process are investigated by analyzing samples withdrawn at different time during the polymerization of HPMA using transmission electron microscopy (TEM) and dynamic light scattering (DLS) at different temperatures (5–70 °C).