Collagen-Mimetic Hydrogels Promote Human Endothelial Cell Adhesion, Migration and Phenotypic Maturation

This work evaluates the response of human aortic endothelial cells (HAECs) to thromboresistant collagen-mimetic hydrogel coatings toward improving the biocompatibility of existing off-the-shelf small-caliber vascular grafts. Specifically, bioactive hydrogels-previously shown to support α1/α2 integrin-mediated cell adhesion but to resist platelet activation-were fabricated by combining poly(ethylene glycol) (PEG) with a 120 kDa, triple-helical collagen-mimetic protein (Scl2-2) containing the GFPGER adhesion sequence. Analysis of HAECs seeded onto the resulting PEG-Scl2-2 hydrogels demonstrated that HAEC adhesion increased with increasing Scl2-2 concentration, while HAEC migration rate decreased over this same concentration range. In addition, evaluation of HAEC phenotype at confluence indicated significant differences in the gene expression of NOS3, thrombomodulin, and E-selectin on the PEG-Scl2-2 hydrogels relative to PEG-collagen controls. At the protein level, however, only NOS3 was significantly different between the PEG-Scl2-2 and PEG-collagen surfaces. Furthermore, PECAM-1 and VE-cadherin expression on PEG-Scl2-2 hydrogels versus PEG-collagen controls could not be distinguished at either the gene or protein level. Cumulatively, these data indicate the PEG-Scl2-2 hydrogels warrant further investigation as off-the-shelf graft coatings. In future studies, the Scl2-2 protein can potentially be modified to include additional extracellular matrix or cytokine binding sites to further improve endothelial cell responses

Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB

Targeted Drug-Resistance Testing Strategy for Multidrug-Resistant Tuberculosis Detection, Lima, Peru, 2005–2008

Running head: Targeted Drug-Resistance Testing Strategy for MDR T

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Lipid profile, plasma apolipoproteins, and pre-eclampsia risk in the GenPE case-control study

Background and aims: Pre-eclampsia constitutes a leading cause of maternal and perinatal morbidity and mortality. Pre-eclampsia susceptibility is believed to be associated with altered lipid profiles and abnormal lipid metabolism via lipid peroxidation that leads to endothelial dysfunction. The goal of this study was to evaluate the association of maternal blood lipid and apolipoprotein levels with pre-eclampsia in a large-scale study. Methods: Using data from a large case-control study (1366 cases of pre-eclampsia and 1741 normotensive controls), the association between the distributions of eight lipid fractions and pre-eclampsia risk was evaluated using adjusted logistic regression models. Pre-eclampsia was defined as blood pressure ≥140/90 mmHg and proteinuria ≥300 mg/24 h (>1 + dipstick). Sub-group analyses were conducted for early (<34 weeks) and late (≥37 weeks) pre-eclampsia, estimating the effect of 1 standard deviation increase in log-transformed lipid fraction levels in adjusted multinomial regression models. Results: After adjustment for potential confounders, concentrations of triglycerides, apolipoprotein E (ApoE) and the relationship between apolipoprotein B and A1 (ApoB/ApoA1) showed the strongest associations with pre-eclampsia, particularly for those cases with an early onset. Conclusions: Higher levels of triglycerides, ApoE and the ApoB/ApoA1 ratio are associated with an increased risk of pre-eclampsia. Further studies that allow for a causal inference are needed to confirm or refute the aetiological role of blood lipids in pre-eclampsia

Signification and Formation of Company´s Internal Guidelines at Organization Parts of the State

Import 01/09/2009Prezenční117 - Katedra účetnictvívýborn